http://www.nice.org.uk National Prescribing Center: Sun WY, Reiser IW, Chou S-Y. Risk factors for acute renal insuf \201 - ciency induced by d iuretics in patients with congestive heart fail- ure. Am J Kidney Dis 2006; 47: 798 \200 \223808. http://www.npc.co.uk/ Voilley N, Bassilana F, Mignon C, et al. Cloning, chromosomal locali- zation, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amilorid e-sen- sitive sodium channel. Genomics 1995; 28: 560 \200\223565. See also Drug-induced nephropathies, p. 698 Nephrotic syndrome, p. 80 Clinical approach to hypertension, p. 286 Medical management of stone disease, p. 270 Vormfelde SV, Sehrt D, Toliat MR, et al. Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol The r 2007; 82: 300 \200\223309. Weber KT. Furosemide in the long-term management of heart fail- ure: the good, the bad and the uncertain. J Am Coll Cardiol 2004; 44: 1308 \200\2231310. This page intentionally left blank J. FREW, C. MCBAIN AND T. ELLIOTT 714 Systemic cancer therapies and the kidney Introduction Many chemotherapeutic agents are \201 ltered by the kidneys with some also u ndergoing tubular secretion. The kidneys are therefore vulnerable to the toxic effects of c ytotoxic drugs with nephrotoxicity often the dose-limiting side- effect in chemotherapeutic regimens. Drug pharmacokinetics may be altered in patients with renal impairment if renal excretion plays a signi \201 cant role in drug elimination. Dose adjustment tailored to pa tients \200\231 renal function is necessary to avoid exposure to excessive drug levels and subsequent toxicity. Clearance of the drug by hemodialysis can lead to decreased drug exposure and therapeutic e f \201 cacy. Dialysable drugs \200 \200 \200 \200 \200 cisplatin carboplatin cyclophosphamide ifosfamide methotrexate. Nephrotoxicity of chemotherapy agents Chemotherapy agents can affect the microvasculature, glomeruli and tubules. Clinical manifestations (examples given below) depend on the site of nephron most adversely affected and include: \200 Assessment of renal function Renal function is assessed prior to chemotherapy dosing. Metho ds include: \200 EDTA-GFR (gold standard: radioisotope to measure GFR); timed urine collection to calculate creatinine clearance: (Urine Cr \227 Urine Vol) (Plasma Cr \227 Time (min)) tubulointerstitial injury causing asymptomatic decrease in GFR; hemolytic microangiopathy r esembling hemolytic uremic syndrome (HUS); tubular dysfunction with electrolyte imbalance; AKI necessitating dialysis. ; CrCl (mL/min) = \200 formulas to estimate GFR. Formulas developed to estimate creatinine clearance are based on point sampling of serum cr eatinine and incorporate patient-related factors including age, weight and gender. Formulas include: \200 \200 \200 \200 \200 Agents causing tubulointerstitial damage Cisplatin Heavy metal alkylating-like agent. Widel y used in many treatment sites including: \200 \200 \200 \200 Cockcroft and Gault (see below); Jeliffe; Wright; Chatelut; Modi \201 cation of Diet in Re nal Disease (MDRD) study formula. (most commonly employed, see Appendix) testicular; gynecological; urological; head and neck cancers. Cisplatin rapidly becomes protein-bound but concentrates in the kidneys by undetermined mec hanisms. 15 \200\22375% cleared in the urine as unchanged drug. Nephrotoxicity is major dos e-limiting side-effect. Cisplatin should be avoided if GFR <30 mL/min. Cisplatin nephrotoxi city manifestations: \200 \200 \200 \200 Prevention of nephrotoxicity: \200 vigor ous prehydration; \200 0.9% saline infusion; aim for urine output >150 mL/h; \200 magne sium replacement as cisplatin-induced hypomag- nesemia potentiates nephrotoxicity; consider mannitol. Formulas require stable creatinine and are in \202 uenced by muscle mass and \202 uid ba lance. Cockcroft and Gault formula (140 \200\223 age) \227 Weight (kg) \227 \200\230Y \200\231 CrCl (mL/min) = Serum Cr (mg/dL) subclinical reduction in GFR with each cycle; AKI; salt-wasting nephropathy; magnesium-wast ing nephropathy. Y = 1.23 in men and 1.04 in women. Chemotherapy The aim of treatment in patients with cancer needs to be clearly de \201 ned. Potential side-effect pro \201 les should be considered in the context of whether treatme nt is curative or palliative. Drugs causing signi \201 cant nephrotoxicity such as meth- o trexate and cisplatin should be avoided in patients with renal insuf \201 ciency. Renal impairment and pharmacokinetics Anticancer drugs can be eliminated from the body thro ugh metabolism, excretion in the urine, bile or feces, or through the respiratory tract. Pa tients with renal dysfunction receiving chemotherapy which is primarily eliminated via the kidneys have decreased clearance in the urine. This results in increased systemic exposure as indicated by increased area under the curve (AUC) of plasma concentration vs time (Table 18.4.1). Carboplatin A second generation platinum agent. Nephrotoxicity is rarely clinically signi \201 cant. Carboplatin dosing is safe in patients with renal impairment. Renal clearance is closely correlated with GFR. The dose is calculated using the Calvert formula (see below), which considers the GFR and desired AUC (normally 4 \200\2237 mg/mL/min). Carboplatin = target AUC \227 (EDTA-GFR + 25) dose (mg) Hemodialysis and chemotherapy There is limited data on the clearance of chemotherapeutic ag ents by dialysis. CHAPTER 18.4 Systemic cancer therapies and the kidney 715 Table 18.4.1 Chemotherapy dosing in patients with renal impairment Mortality 50%. Gemcitabine A nucleoside analog which interferes with DNA synthesis. It is used in breast, bladder, lung, gastrointestinal, gyneco- logical and germ cell tumors. Mild proteinuria and microscopic hematuria occur in up to 50% of patients and elevated creatinine in 8%. It rar ely develops into profound HUS with no clear rela- tionship between dose or time interval p ost therapy. Bleomycin Capecitabine Cisplatin Carboplatin Dacarbazine Etoposide Epirubicin Fludarabine Ifosfamide Irinotecan Melphalan Methotrexate Nitrosoureas Raltitrexed Drugs requiring dose adjustment Docetaxel Drugs not generally requiring dose adjustment Fluorouracil Agents causing urinary tract obstruction Ifosfomide and cyclophosphamide Gemcitabine Oxaliplatin Both drugs can cause obstruction secondary to hemorrhagic cystitis. This complication is ca used by metabolites including acrolein excreted in the urine. Prevention: \200 \200 Methotrexate (MTX) An antifolate drug which depletes cellular tetrahydro- folate. High dose MTX (1 \200\22312 g/m2) is used in the treatment of CNS lymphoma and osteosarcomas. It is exclusively eliminated via the kidneys. Parent drug and metabolite are highly insoluble in acid and urine. Toxicity is related to level and duration of elevated MTX levels. AKI can o ccur due to precipitation of drug within tubules and potentially a direct nephrotoxic effec t. Normally it is self-limiting with recovery over 12 7 days. Prevention of nephrotoxici ty: adequte hydration; IV bicarbonate (alkalinize urine); leukovorin rescue (tetrahydrofoli c acid derivative) com- mencing 24 \200\22336 h post MTX. vigorous hydration and frequent bladder emptying; IV Mesna \233\232 (binds acrolein to prod uce nontoxic com- pound). Biological and targeted therapies There has been a marked increase in the use of biological therapies in cancer management over recent years. The side-effect profiles of most of thes e therapies are favorable compared to conventional cytotoxic chemotherapy. Monoclonal antibodies Humanized monoclonal antibodies are directed against a variety of pro teins including: \200 growth factor receptors; \200 angiogenesis-promoting factors; \200 tumor cell surface antigens. \200 \200 Ifosfamide An alkylating drug similar to cyclophosphamide. Indications include sarcomas and hematological cancers. Side-effects: nephrotoxicity, neurotoxicity and myelosup- pression. Ifosfamide and cyclophosphamide can also cause hemor- rhagic cysitis. Ifosfamide can cause tubular injury presenting with Fanconi \200\231s anemia: \200 \200 \200 \200 \200 Nephrotoxicity is rare and not usually of clinical signi \201 cance with these agents. Bevacizumab A monoclonal antibody to vascular endothelial growth factor (VEGF). Hypertensio n, proteinuria and rarely nephritic syndrome have been reported. Renal biopsy demonstrates an immune-complex-mediated glomerulonephritis. hyperchloremic metabolic acidosis; hypophosphatemia; hypokalemia; renal glycosuria; aminoac iduria. Tyrosine kinase inhibitors Tyrosine kinase inhibitors are metabolized in the liver with exc retion predominantly in the feces. Dose reduction not usually required but multiple new agents are in development and each mus t be assessed individually. Agents causing hemolytic uremic syndrome Mitomycin C (MMC) An alkylating antibiotic used in the treatment of breast, gastrointestinal, pancreatic and lung cancers. MMC nephrotoxicity normally presents with HUS 6 \200\22320 months after initiation of chemotherapy. There is a classical triad of: \200 \200 \200 Immune response modi \201 ers Interferon An antiviral and antineoplastic agent which modi \201 es the host response to cancer (e.g. renal cell carcinoma and melanoma). It has a spe ctrum of renal toxicity from mild elevation of creatinine and proteinuria to nephrotic synd rome and AKI (rare). microangiopathic hemolytic anemia; thrombocytopenia; AKI. It is dose dependent, usually occurring after a cumulative dose >60 mg/m2. J. FREW, C. MCBAIN AND T. ELLIOTT 716 Other drugs Bisphosphonates These are potent inhibitors of osteoclast-mediated bone resorpt ion. They are used in the treatment and prevention of bone metastasis in breast and prostat e cancer and also in the treatment of hypercalcemia of malignancy. Dose-dependent renal tub ular injury occasionally develops after several months of treatment and is recognized by an asymptomatic elevation in serum creatinine. Souhami RL, Tannock I, Hohenberger P, Horiot J-C. Oxford textbook of oncology. Oxford: Oxford University Press; 2002. Internet resources Clinical Oncology Information Network (COIN): http://www.rcr.ac.uk/index.asp?pageid=148 Cancerbackup: http://www.cancerbackup.org.uk/home Epocrates ONLINE provides continually updated infor- mation on brand and generic drugs (dosing, drug \200\223drug interactions, adverse reaction s and mode of action: NSAIDs These analgesics are used widely in cancer pain manage- ment. Adverse renal effects include AKI, nephrotic syndrome, hyperkalemia and papillary necrosis. http://www.epocrates.com See also Drug-induced nephropathies, p. 698 Cancer and the kidney, p. 196 Clinical approach to acute kidney injury, p. 318 Further reading Cohen EP. Cancer and the kidney. Oxford: Oxford University Press; 2005. COIN Guidelines. Renal function and chemotherapy. Clin Oncol 2001; 13: S222. Fischer DS, et al. The cancer chemotherapy handbook, 6th edn. St Louis: Mosby; 2003. Kintzel PE. Anticancer drug-induced kidney disorders. Drug Safety 2001; 24: 19 \200\22338. 717 Appendix Anatomy of the kidney and nephron 718 Calculations for acid \200\223base balance and extrac ellular \202 uid volume 720 Calculations of the glomerular \201 ltration rate 722 Relat ionship of glomerular \201 ltration rate with age 723 Calculations of dialysis adequacy 7 24 Classi \201 cation of chronic kidney disease 726 Internet resources 727 Professional so cieties 728 Clinical practice guidelines and renal registries 729 Information resources for professionals 730 Information resources for patients and carers 731 Patient counseling too ls 732 Biochemistry conversion table 735 APPENDIX 718 Anatomy of the kidney and nephron Gross anatomy of the kidney 2 1 3 6 Ureter 7 Pelvis of the kidney 8 Renal vessels 9 Hilum 10 Calyx 1 Parenchyma 2 Cortex 3 Medulla 4 Perirenal fat 5 Capsule 10 4 9 8 7 5 6 Anatomical divisions of the nephron 9 8 9* The drawing (not to scale) depicts a short-looped (superficial) and a long-looped (juxtamed ullary) nephron. Within the cortex, a dashed line delineates a medullary ray. 1 Renal corpu scle, including glomerulus and Bowman s capsule 2 Proximal convoluted tubule 3 Proximal str aight tubule (pars recta) 4 Thin descending limb 5 Thin ascending limb 6 Thick ascending li mb 7 Macula densa 8 Distal convoluted tubule 9 Connecting tubule 9* Connecting tubule of ju xtamedullary nephron that forms an arcade 10 Cortical collecting tubule 11 Outer medullary collecting duct 12 Inner medullary collecting duct 1 2 7 Cortex 8 1 10 7 2 3 6 3 Outer stripe a l l u d e m 6 Inner stripe 11 4 r e t u O 12 Inner medulla 4 5 Reproduced with permission from Davison AMA, Cameron JS, Grunfeld J-P et al. (eds) (2005) O xford Textbook of Nephrology, 3rd edn. Oxford: Oxford University Press. 719 APPENDIX Microanatomy of the glomerulus The renal corpuscle and juxtaglomerular apparatus The capillary tuft consists of a network of specialized capil- laries, which are outlined by a fenestrated endothelium (E). At the v ascular pole an afferent arteriole (AA) enters and an efferent arteriole (EA) leaves the tu ft. The capillary net- work is surrounded by Bowman \200\231s capsule, comprising two diffe rent epithelia: the visceral and the parietal epithelium. The visceral epithelium consists of highly branched podo- cytes (PO) and directly follows, together with the glomer- ular ba sement membrane (GBM), the surface of the capillaries and the mesangium (M). At the vascula r pole, the visceral epithelium and the GBM are re \202 ected into the parietal epithelium (PE) of Bowman \200\231s capsule (and its base- ment membrane), which passes over into the epithelium of the proximal tubule (PT) at the urinary pole. Mesangial cells (M) are situat ed in the axes of glomerular lobules. At the vascular pole the glomerular mesangium is cont inuous with the extraglomerular mesangium (EGM), consisting of cells and matrix. The EGM, t ogether with the terminal portion of the afferent arteriole containing the granular cells ( G), the efferent arteriole, and the macula densa (MD), establish the juxta- glomerular appa ratus. F, foot processes; N, sympathetic nerve terminals; US, urinary space. Electron micrograph of a glomerular lobule The capillary (C) is outlined by a \202 at fen estrated endothe- lium (E). The podocyte layer (PO) and the glomerular basement membrane (G BM) do not encircle the capillary completely, they form a common surface cover around the e ntire lobule. In the peripheral portion of the capillary the \201 ltration bar- rier is f ormed (see below). Two subdomains of the GBM are delineated from each other by mesangial an gles (arrows): the pericapillary GBM (cGBM) faced by the podocyte and endothelial layer, an d the perimesangial GBM (mGBM) bordered by the podo- cyte layer and the mesangium. Within t he mesangium two types of mesangial cells are shown: contractile mesangial cells proper (M) and a cell ( \210\227) that is probably a macrophage that has invaded the mesangium. US, u rinary space. Electron micrograph of the \201 ltration barrier The peripheral part of the glomerular ca pillary wall com- prises the fenestrated endothelial layer (E), the GBM, and the interdigit ating foot processes (F). The \201 ltration slits between the foot processes are bridged by thin diaphragms (long arrows). Arrowheads point to the endothelial pores. The GBM shows a lamina densa (2) bounded by the lamina rara interna (1) and the lamina rara externa (3). C, capillary lumen. APPENDIX 720 Calculations for acid \200\223base balance and extracellular \202 uid volume Renal and respiratory compensation for primary acid \200\223base disturbances Disorder Primary change Compensatory response \200\223] Metabolic acidosis 0.16 kPa (1.2 mmHg) decrease in PCO2 per 1 mmol/L decrease in [HCO3 \206\223 [HCO3 \200\223] \206\221 [HCO3 \200\223] \206\221 PCO2 \200\223] 0.093 kPa (0.7 mmHg) increase in PCO2 per 1 mmol/L increase in [HCO3 Metabolic alkalosis Respiratory acidosis Acute Chronic \200\223] per 1.33 kPa (10 mmHg) increase in PCO2 1 mmol/L increase in [HCO3 3.5 mmol/L increase in [HCO3 \200\223] per 1.33 kPa (10 mmHg) increase in PCO2 Respiratory alkalosis Acute Chronic \206\223 PCO2 \200\223] per 1.33 kPa (10 mmHg) decrease in PCO2 \200\223] per 1.33 kPa (10 mmHg) decrea se in PCO2 2 mmol/L decrease in [HCO3 4 mmol/L decrease in [HCO3 Metabolic acidosis Serum anion gap (AG) [Na+] \200\223 [HCO3 or [Na+] + [K+] \200\223 [HC O3 \200\223] \200\223 [Cl \200\223] (normal range 12 2) \200\223] \200\223 [Cl \200\223] (normal range 16 2) Normal AG metabolic acidosis Increased AG metabolic acidosis \200 \200 Renal tubular acidosis (types 1, 2, and 4) Diarrhea and other intestinal losses (e.g. bilia ry or pancreatic drainage) Carbonic anhydrase inhibitors Ureteral diversion (e.g. ileal con duit) Toluene ingestion Lactic acidosis Ketoacidosis \200 diabetic \200 alcohol-associated \200 starvation In gestions \200 methanol \200 ethylene glycol \200 aspirin Renal failure \200 \200 Serum osmolal gap (OG) Measured \200\223 calculated osmolality (2[Na+] + [glucose] + [urea ]). Normal OG <10 mosm/L. In the presence of metabolic acidosis, an OG >10 mosm/L suggests the presence of methanol or ethylene glycol. Urine anion gap (to differentiate causes of normal gap metabolic acidosis) Urine [Na+] + [K +] \200\223 [Cl \200\223] \200 \200 Positive value = lack of ammonium in urine = Type 1 RTA, Type 4 RTA Negative value = presen ce of ammonium in urine = All other causes Calculations for the evaluation of disorders of water balance To calculate the sodium requi rement (in mmol) for a patient with hyponatremia TBW \227 (desired serum [Na+] \200\223 actual serum [Na+]) To calculate the water excess (in liters) in a patient with hyponatremia \210\222 1 ] + [ Na + actual serm \227 TBW desired serum [ Na ] To calculate the change in serum [Na+] after 1 liter of IV \202 uid is infused + mm [Na ] \210\222 + [Na ] concentration in IV fluid actual seru TBW + 1 721 APPENDIX To calculate the water de \201 cit (in liters) in a patient with hypernatremia 1 \210\222 + actual serum [Na ] + desired serum [Na ] \227 TBW Total body water (in liters) is estimated as body weight multiplied by 0.6 in men and by 0. 5 in women. APPENDIX 722 Calculations of the glomerular \201 ltration rate Creatinine clearance \227 (U V) creat CrCl = \227 (P f) creat Creatinine clearance in mL/min. Where \200 \200 \200 \200 Ucreat is the urinary creatinine concentration (mmol/L) V is the volume of collected urine (mL) Pcreat is the plasma creatinine concentration ( mol/L) t is the collection time (min) Estimates of GFR (eGFR) The Cockcroft \200\223Gault formula \210\222 \227 (140 age) lean body weight = eGFR 72 \227 44) (P /88. creat eGFR in mL/min where \200 \200 Lean body weight is in kg Pcrea is the plasma creatinine concentration ( mol/L) The MDRD (Modi \201 cation of Diet in Renal Disease) Study formulas Four-variable (most wi dely used) eGFR = 186 \227 (Pcreat/88.4) \200\2231.154 \227 (age) \200\2230.203 \227 (0. 742 if female) \227 (1.21 if Black) eGFR in mL/min/1.73 m2 where \200 \200 Pcreat is the plasma creatinine concentration ( mol/L) Age is in years Six-variable (original formula) eGFR = 170 \227 (Pcreat/88.4) \200\2230.999 \227 (age) \200\2230.176 \227 (Purea/0.166) \200\2230.170 \227 (Palb)+0.318 \227 (0.762 if female) \227 (1.18 if Black) eGFR in mL/min/1.73 m2 where \200 \200 \200 \200 Pcreat is the plasma creatinine concentration ( mol/L) Purea is the plasma urea concentrat ion (mmol/L) Palb is the plasma albumin concentration (g/dL) Age is in years. 723 APPENDIX Relationship of glomerular \201 ltration rate with age GFR is constant up to the age of 40 years and then declines at the rate of 9 mL/min/1.73 m2 per decade. \200 \200 \200 Mean GFR (solid black line). Outer dashed lines show the +2 population standard deviation l imits. The gray line shows the safety limit for living donation of 86 mL/min/1.73 m2 for yo ung adults declining to 50 mL/min/1.73 m2 at age 80 years. The reference plot is based on an analysis of data for 428 live renal transplant donors who had [51Cr]ETDA GFR measure- ments performed according to the method described in the Briti sh Nuclear Medicine Society GFR guidelines. Reproduced with permission from: United Kingdom Guidelines for Living Donor Kidney Transplantation (http://www.bts. org.uk). APPENDIX 724 Calculations of dialysis adequacy Hemodialysis Formulas for quantifying urea removal on hemodialysis and hemodia \201 ltrati on. For the slow \202 ow method of blood sampling eKt/V = Kt/V \200\223 (0.6(Kt/V)/t) + 0.03 where \200 \200 Urea reduction ratio The urea reduction rate (URR) is measured as follows: URR = (1 \200 \223 R) \227 100% where \200 \200 \200 Kt/V is as in formula for spKt/V t is time on dialysis in hours. Urea kinetic modeling (Formal UKM) This requires multiple data inputs to a computer to calc ulate Kt/V by iteration, which makes this method less practical in busy renal units. It req uires the following data: \200 R is the ratio of Ureapost/Ureapre Ureapost is postdialysis blood urea concentration Ureapr e is the predialysis blood urea concentration. measurement of pre- and postdialysis blood urea concen- trations; record of blood and dialy zate \202 ow rates and the dialyser used; measurement of weight loss during dialysis; mea surement of urea removal in the interdialytic urine collection; measurement of predialysis blood urea concentration from the subsequent dialysis session. Single pool Kt/V spKt/V urea may be estimated by the second generation equation described a nd validated by Daugirdas: spKt/V urea = \200\223Ln(R \200\223 0.008 \227 t) + (4 \200 \223 3.5 \227 R) \227 UF/W where \200 \200 \200 \200 \200 \200 Ln is the natural logarithm R is the ratio of Ureapost/Ureapre t is the dialysis session le ngth in hours UF is the ultra \201 ltration volume in liters W is the postdialysis weight in kilograms. Further reading Daugirdas JT, Schneditz D. Overestimation of hemodialysis dose depends on d ialysis ef \201 ciency by regional blood \202 ow but not by conventional two pool kineti c analysis. ASAIO J 1995; 41: M719 \200\223 M724. Direct measurement of equilibrated Kt/V urea (eKt/V) The single pool model equation does not allow for tissue rebound of blood urea and can be u sed with a 30 min post- dialysis blood urea concentration to calculate equilibrated Kt/V ur ea (eKt/V): eKt/V = \200\223Ln(R30 min \200\223 0.008 \227 t) + (4 \200\223 3.5 \227 R 30 min) Daugirdas JT. Second generation logarithmic estimates of single- pool variable volume Kt/V; an analysis of error. J Am Soc Nephrol 199; 4: 1205 \200\2231213. Geddes CC, Traynor J P, Walbaum D, et al. A new method of post- dialysis blood urea samplin g: the \200\234stop dialysate \202 ow \200\235 method. Nephrol Dial Transplant 2000; 15: 517 \200\223523. \227 UF/W where \200 \200 \200 \200 \200 Gotch FA, Sargent JA. A mechanistic analysis of the National Cooperative Dialysis Study (NC DS). Kidney Int 1985; 28: 526 \200\223534. Ln is the natural logarithm R30 min is the ratio of 30 min Ureapost/Ureapre t is the dialys is session length in hours UF is the ultra \201 ltration volume in liters W is the postdia lysis weight in kilograms. Owen WF, Lew NL, Lowrie EG, et al. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing haemodialysis. N Eng J Med 1993; 329: 10 01 \200\2231006. Priester-Coary A, Daugirdas JT. A recommended technique for Estimation of equilibrated Kt/V (eKt/V) Most HD patients do not wish to wait 30 min after t he end of HD to have a blood sample taken and so formulas have been developed to predict th e 30 min blood urea concentration. Formulas for estimating eKt/V have been derived for the stop dialyzate \202 ow and slow \202 ow methods of postdialysis blood sampling. Both me thods were derived and validated in HD patients by direct comparison with the gold standard of using a measured 30 min postdialysis blood urea concentration to calculate eKt/V. obtaining the post dialysis BUN. Semin Dial 1997; 10: 23 \200\22325. Traynor JP, Geddes CC, Ferguson C, Mactier RA. Predicting 30- minute post-dialysis blood ur ea concentration using the stop dialysate \202 ow method. Am J Kidney Dis 2002; 39: 308 \200\223314. Online adequacy calculators http://www.kt-v.net/ http://www.hdcn.com/calcf/dzer.htm Peritoneal dialysis Weekly dialysis creatinine clearance \227 (D D vol) = \227 \227 7 creat For the stop dialyzate \202 ow method of blood sampling eKt/V = \200\223Ln(R30 min \200 \223 0.008 x t) + (4 \200\223 3.5 \227 R30 min) (1.73/BSA) CrCl P creat \227 UF/W Creatinine clearance in L/1.73 m2/week where \200 where \200 R30 min is estimated from the 5 min postdialysis blood urea concentration obtained by the s top dialyzate \202 ow method R30 min is the ratio of estimated 30 min (e30 min) Ureapost/ Ureapre e30 min Ureapost = 1.06 \227 (5 min Ureapost) + 0.22. Dcreat is the dialyzate creatinine concentration (cor- rected for glucose) Pcreat is the pl asma creatinine concentration BSA is body surface area D vol is the dialyzate volume in lit ers. \200 \200 725 APPENDIX where \200 \200 Weekly residual renal creatinine clearance weight is in kg height is in cm. (Ucreat \227 Uv)] [(Uurea \227 Uv) + Pcreat Purea CrCl = \227 (1.73/BSA) \227 (7/2) Total body water V as estimated by the Watson equation: Creatinine clearance in L/1.73 m2/week where \200 \200 \200 \200 \200 Males V = 2.447 \200\223 (0.09516 \227 age) + (0.1074 \227 height) Uurea is the urine urea concentration Uv is the urine volume Purea is the plasma urea conce ntration Ucreat is the urine creatinine concentration Pcreat is the plasma creatinine conce ntration. + (0.3362 \227 weight) Females V = 2.097 + (0.1069 \227 height) + (0.2466 \227 weight) where \200 \200 \200 Total weekly creatinine clearance weight is in kg height is in cm age is in years. Weekly dialysis + Weekly residual renal CrCl CrCl Creatinine clearance in L/1.73 m2/week. W eekly dialysis Kt/Vurea Kt/V = (Durea \227 Dialyzate volume/Purea) \227 (7/V) where \200 \200 \200 Normalized protein equivalent of total nitrogen appearance nPNA as estimated by the Randers on equation: nPNA = [10.76 (UNA/1.44 + 1.46)]/body weight where \200 Durea is dialyzate urea concentration Purea is the plasma urea concentration V is the patie nt \200\231s total body water (see below). UNA is the urea appearance in dialyzate and urine in g/day. Alternatively the nPNA can be calculated using: nPNA = 5.02 \227 [(UGR \227 60.06) + 3.12 ]/body weight where \200 Weekly residual renal Kt/Vurea Kt/V = (Uurea \227 Urine volume/Purea) \227 (7/V) where \200 \200 \200 UGR is the urea generation rate in mmol/min. Uurea is the urine urea concentration Purea is the plasma urea concentration V is the patie nt \200\231s total body water (see below). Further reading Lysaght MJ, Farrell PC. Membrane phenomena and mass transfer kinetics in peritoneal dialysis. J Membr Sci 1989; 44: 5 \200\22333. Total weekly Kt/Vurea Weekly dialysis + Weekly residual renal Kt/Vurea Body surface area Du bois method: BSA = 0.007184 \227 (height \227 0.725) \227 (weight \227 0.425) Lysaght MJ, Pollock CA, Hallet MD, Ibels LS, Farrell PC. The rele- vance of urea kinetic mo deling to CAPD. ASAIO Trans 1989; 35: 784 \200\223790. Kt/Vurea Online adequacy calculators http://www.kt-v.net/ http://www.hdcn.com/calcf/dzer.htm APPENDIX 726 Classi \201 cation of chronic kidney disease Classi \201 cation of CKD based on the NKF K/DOQI recommendations GFR (mL/min/1.73 m2) CKD stage Description Kidney damage with a normal or increased GFR There must be other evidence of kidney damage: \200 persistent microalbuminuria \200 persistent proteinuria \200 persistent hematur ia \200 structural abnormalities of the kidneys demonstrated \200 on USS or other radio logical tests \200 biopsy-proven chronic glomerulonephritis Kidney damage with mild reduc tion in GFR There must be other evidence of kidney damage (as above) >90 1 60 \200\22389 2 Moderate reduction in GFR 30 \200\22359 3 Severe reduction in GFR 15 \200\22329 4 Kidney failure <15 (or dialysis) 5 This classi \201 cation is based on the NKF K/DOQI recommendations. http://www.kidney.org/professionals/kdoqi/index.cfm Proposed changes according to the draft NICE National Clinical Guideline for the Management of Adults with Chronic Kidney Disease It has been proposed that the suf \201 x P should b e used to denote the presence of proteinuria when staging CKD: For this purpose proteinuria is de \201 ned as: \200 \200 urinary albumin to creatinine ratio \211 30 mg/mmol urinary protein excretion \211 0.5 g/ 24 h Stage 3 should be split into two subcategories de \201 ned by: \200 \200 GFR 45 \200\22359 mL/min/1.73 m2 GFR 30 \200\22344 mL/min/1.73 m2 CKD stage 3A CKD stage 3B http://www.nice.org/guidance/index.jsp?action=download&o=39959 727 APPENDIX Internet resources Journals Advances in Chronic Kidney Disease An of \201 cial Journal of the National Kidney Federation: Kidney and Blood Pressure Research http://content.karger.com/ProdukteDB/produkte. asp?Aktio n=JournalHome&ProduktNr=224258 Kidney International Journal of the International Society of Nephrology: http://journals.elsevierhealth.com/periodi- cals/xackd http://www.nature.com/ki/index.html American Journal of Kidney Diseases Journal of the National Kidney Federation: Nature Clinical Practice Nephrology http://www.nature.com/ncpneph/index.html http://www.ajkd.org/ Nephrology Journal of the Asian Paci \201 c Society of Nephrology: American Journal of Nephrology http://content.karger.com/ProdukteDB/produkte. asp?Aktion=Jo urnalHome&ProduktNr=223979 http://www.blackwellpublishing.com/journal. asp?ref=1320-5358&site=1 American Journal of Physiology \200\223 Renal Physiology Journal of the American Physiolog ical Society: Nephrology Dialysis and Transplantation Journal of the European Renal Association \200\223 European Dialysis and Transplant Association: http://ajprenal.physiology.org/ American Journal of Transplantation Journal of the American Society of Transplant Surgeons and the American Society of Transplantation: http://ndt.oxfordjournals.org/ Nephron Journals Incorporating: \200 \200 \200 http://www.blackwellpublishing.com/journal. asp?ref=1600-6135 Nephron Clinical Practice Nephron Experimental Nephrology Nephron Physiology British Journal of Renal Medicine http://www.bjrm.co.uk/bjrm/ http://content.karger.com/ProdukteDB/produkte. asp?Aktion=JournalHome&ProduktNr=223854 Clinical and Experimental Nephrology Journal of the Japanese Society of Nephrology: Pediatric Nephrology Journal of the International Pediatric Nephrology Association: http://www.springerlink.com/content/103835/ Clinical Journal of the American Society of Nephrology An of \201 cial Journal of the Amer ican Society of Nephrology: http://link.springer-ny.com/link/service/jour- nals/00467/ index.htm http://cjasn.asnjournals.org/ Pediatric Transplantation Journal of the International Pediatric Transplant Association: Clinical Nephrology http://www.clinnephrol.com http://www.blackwellpublishing.com/journal. asp?ref=1397-3142&site=1 Clinical Transplantation http://www.blackwellpublishing.com/journal. asp?ref=0902-0063 Peritoneal Dialysis International Journal of the International Society for Peritoneal Dialy sis: Current Opinion in Nephrology and Hypertension http://www.co-nephrologyandhypertension.com http://www.pdiconnect.com/ Renal Failure http://www.informaworld.com/smpp/title db=all content=t713597293 tab=issuesl ist Experimental and Clinical Transplantation http://www.ectrx.org/ Hypertension, Dialysis and Clinical Nephrology An of \201 cial educational program of the Renal Physicians Association and American Society of Nephrology: Seminars in Nephrology http://www.seminarsinnephrology.org/ Seminars in Dialysis http://www.blackwellpublishing.com/journal. asp?ref=0894-0959&site=1 http://www.hdcn.com/ Journal of Nephrology Journal of the Italian Society of Nephrology: Journal of Renovascular Disease http://www.journalrenovasculardisease.com http://www.jnephrol.com/index.asp?a= current Journal of the American Society of Nephrology http://jasn.asnjournals.org/ Transplantation Journal of the Transplantation Society: http://www.transplantjournal.com/ APPENDIX 728 Professional societies American Society for Arti \201 cial Organs http://www.asaio.com/ European Kidney Health Alliance http://www.ekha.eu/ American Society of Diagnostic and Interventional Nephrology http://www.asdin.org/ European Society for Organ Transplantation http://www.esot.org/ International Pediatric Transplant Association http://www.iptaonline.org/ American Society of Nephrology http://www.asn-online.org/ International Society for Hemodialysis http://www.ishd.net/ American Society of Pediatric Nephrology http://www.aspneph.com/ International Society of Blood Puri \201 cation http://www.isbp.org American Society of Transplantation http://www.a-s-t.org/ International Society of Nephrology http://www.nature.com/isn/index.html Asian Paci \201 c Society of Nephrology http://www.apsneph.org/ International Society of Peritoneal Dialysis http://www.ispd.org/ Association of Renal Technologists (UK) http://www.artery.org.uk/site/ART/home International Society of Renal Nutrition and Metabolism http://www.renalnutrition.com/ Australia and New Zealand Society of Nephrlology http://www.nephrology.edu.au/ National Kidney Foundation (US) http://www.kidney.org/ British Association for Pediatric Nephrology http://www.bapn.org/ Renal Association, UK http://www.renal.org/pages/ British Renal Society http://www.britishrenal.org/ Renal Pathology Society http://www.renalpathsoc.org/ British Society for Histocompatibility and Immunogenetics http://www.bshi.org.uk/ Renal Physicians Association (US) http://www.renalmd.org/ British Transplantation Society http://www.bts.org.uk/ The Transplantation Society http://www.transplantation-soc.org/ Canadian Society of Nephrology http://www.csnscn.ca/ UK Transplant http://www.uktransplant.org.uk/ Commission for the Global Advancement of Nephrology http://www.nature.com/isn/society/outre ach/ index.html Vascular Access Society (UK) http://www.vascularaccesssociety.com/ European Renal Association \200\223 European Dialysis and Transplant Association http://ww w.era-edta.org/ 729 APPENDIX Clinical practice guidelines and renal registries ANZDATA Australia and New Zealand Dialysis and Transplant Registry http://www.anzdata.org.a u/ANZOD International Federation of Renal Registries http://www.ifrr.net/ Israel Penn Transplant Tumor Registry: http://www.ipittr.uc.edu/Home.cfm Australian and New Zealand Organ Donation Registry http://www.anzdata.org.au/anzod/anzodwel come.htm K/DOQI Guidelines (USA) Kidney Disease Outcomes Quality Initiative http://www.kidney.org/pr ofessionals/kdoqi/ index.cfm British Transplantation Society Guidelines http://www.bts.org.uk/standards.htm Kidney Disease: Improving Global Outcomes (KDIGO) http://www.kdigo.org/ CARI Guidelines (Australian) http://www.cari.org.au/ Canadian Registry http://secure.cihi.ca/cihiweb/splash.html Renal Association (UK) Clinical Practice Guidelines http://www.renal.org/pages/pages/clinic al- affairs/guidelines.php Canadian Society of Nephrology Guidelines http://www.csnscn.ca/english/professional %20prac tice/programs/default.asp?s=1 Scottish Renal Registry http://www.srr.scot.nhs.uk/ Collaborative Transplant Study http://www.ctstransplant.org/ UK Renal Registry http://www.renalreg.com/ Dialysis Outcomes and Practice Patterns Study D.O.P.P.S Study http://www.dopps.org/ United States Renal Data System http://www.usrds.org/ European Renal Registry http://www.era-edta-reg.org/index.jsp United States Transplant Registry http://www.ustransplant.org Eurotransplant http://www.transplant.org/ Guidelines of the European Best Practice Group of the ERA \200\223EDTA http://www.ndt-educa tional.org/ APPENDIX 730 Information resources for professionals Atlas of Diseases of the Kidney http://www.kidneyatlas.org/ Kidney School http://www.kidneyschool.org/ Calculation tools for nephrologists Dialysis adequacy tools http://www.kt-v.net/ Family Practice Notebook http://www.fpnotebook.com/REN.htm Medmark http://www.medmark.org/neph/nep2.html http://www.hdcn.com/calcf/dzer.htm eGFR calculator http://www.renal.org/eGFRcalc/GFR.pl National Institute for Health and Clinical Excellence http://www.nice.org.uk Renal SI Conversion Center http://nephron.com/cgi-bin/SI.cgi National Institute of Diabetes & Digestive & Kidney Diseases (US) http://www.niddk.nih.gov/ index.htm Cochrane Renal Group http://www.cochrane-renal.org/ CyberNephrology http://www.kidney.org/professionals/cyber/ index.cfm# NDT Educational http://www.ndt-educational.org/Nephrology Nephrology Rounds http://www.nephrologyrounds.org East Midlands Renal Network http://www.eastmidlandsrenalnetwork.org.uk/ Nephron Information Center http://nephron.com/ EdREN, the website of the Renal Unit at the Royal In \201 rmary of Edinburgh www.edren.org NephrOnline http://www.nephronline.org/ European Uraemic Toxin (EUTox) work group of the European Society of Arti \201 cial Organs http://www.uremic-toxins.org/ PREVEND Study (Prevention of Renal and Vascular End-Stage Disease) http://www.prevend.org/ Great Ormond Street Hospital http://www.gosh.nhs.uk/clinical_information/ RenalNet http://www.renalnet.org/ Kidney Disease Quality of Life Working Group http://www.gim.med.ucla.edu/kdqol/ Renal Resource Center http://www.renalresource.com/ Kidney Health Australia http://www.kidney.org.au/ RenalWEB http://www.renalweb.com/ Kidney & Urologic Disease Dictionary Index http://kidney.niddk.nih.gov/kudiseases/a-z.asp UKidney \200\223Internet School of Nephrology http://ukidney.com/ 731 APPENDIX Information resources for patients and carers Associations American Association of Kidney Patients http://www.aakp.org/ The Kidney Patient Guide http://www.kidneypatientguide.org.uk/ The Kidney School http://www.kidneyschool.org/ British Organ Donor Society http://body.orpheusweb.co.uk/index.html National Kidney Disease Education Program http://www.nkdep.nih.gov/ Diabetes UK http://www.diabetes.org.uk/ Transplantation Living Kidney Donors \200\231 Experiences http://www.transweb.org/people/li ve_don.htm European Kidney Health Alliance http://www.ekha.eu/ European Kidney Patients Federation http://www.ceapir.org/HP/ Transplants in Mind http://www.transplantsinmind.org.uk/ European Transplant and Dialysis Sport Federation http://www.etdsf.org/ TransWeb http://www.transweb.org/ The Transplant Support Network http://www.transplantsuppo rtnetwork.org.uk/ International Federation of Kidney Foundations http://www.ifkf.net/ National Kidney Federation (US) http://www.kidney.org/patients/