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BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN) have high rates of premature death. OBJECTIVE: To assess the potential effect on survival of renal transplant among patients with ESRD due to LN (LN-ESRD) in the United States. DESIGN: Nationwide cohort study. SETTING: United States Renal Data System, the national database of nearly all patients with ESRD. PARTICIPANTS: Patients with incident LN-ESRD who were waitlisted for a renal transplant. MEASUREMENTS: First renal transplant was analyzed as a time-varying exposure. The primary outcomes were all-cause and cause-specific mortality. Time-dependent Cox regression analysis was used to estimate the hazard ratio (HR) of these outcomes associated with renal transplant in the primary analysis. Sequential cohort matching was used in a secondary analysis limited to patients with Medicare, which allowed assessment of time-varying covariates. RESULTS: During the study period, 9659 patients with LN-ESRD were waitlisted for a renal transplant, of whom 5738 (59%) had a transplant. Most were female (82%) and nonwhite (60%). Transplant was associated with reduced all-cause mortality (adjusted HR, 0.30 [95% CI, 0.27 to 0.33]) among waitlisted patients. Adjusted HRs for cause-specific mortality were 0.26 (CI, 0.23 to 0.30) for cardiovascular disease, 0.30 (CI, 0.19 to 0.48) for coronary heart disease, 0.41 (CI, 0.32 to 0.52) for infection, and 0.41 (CI, 0.31 to 0.53) for sepsis. LIMITATION: Unmeasured factors may contribute to the observed associations; however, the E-value analysis suggested robustness of the results. CONCLUSION: Renal transplant was associated with a survival benefit, primarily due to reduced deaths from cardiovascular disease and infection. The findings highlight the benefit of timely referral for transplant to improve outcomes in this population. PRIMARY FUNDING SOURCE: National Institutes of Health.

Acute kidney injury is a heterogeneous group of conditions characterized by a sudden decrease in glomerular filtration rate, manifested by an increase in serum creatinine concentration or oliguria, and classified by stage and cause. This type of injury occurs in approximately 20% of hospitalized patients, with major complications including volume overload, electrolyte disorders, uremic complications, and drug toxicity. Management includes specific treatments according to the underlying cause and supportive treatment to prevent and manage complications. Kidney replacement therapy is used when complications cannot be managed with medical therapy alone. Despite advances in care, the mortality rate in patients requiring kidney replacement therapy remains approximately 50%.

Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay.To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft-Gault equations.Comparison of estimated and measured GFR.15 clinical centers participating in a randomized, controlled trial.1628 patients with chronic kidney disease participating in the MDRD Study.Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate.Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft-Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m2 or greater.The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a separate study sample.The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates.

Clinical laboratories are increasingly reporting estimated glomerular filtration rate (GFR) by using serum creatinine assays traceable to a standard reference material.To review the performance of GFR estimating equations to inform the selection of a single equation by laboratories and the interpretation of estimated GFR by clinicians.A systematic search of MEDLINE, without language restriction, between 1999 and 21 October 2011.Cross-sectional studies in adults that compared the performance of 2 or more creatinine-based GFR estimating equations with a reference GFR measurement. Eligible equations were derived or reexpressed and validated by using creatinine measurements traceable to the standard reference material.Reviewers extracted data on study population characteristics, measured GFR, creatinine assay, and equation performance.Eligible studies compared the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations or modifications thereof. In 12 studies in North America, Europe, and Australia, the CKD-EPI equation performed better at higher GFRs (approximately60 mL/min per 1.73 m(2)) and the MDRD Study equation performed better at lower GFRs. In 5 of 8 studies in Asia and Africa, the equations were modified to improve their performance by adding a coefficient derived in the local population or removing a coefficient.Methods of GFR measurement and study populations were heterogeneous.Neither the CKD-EPI nor the MDRD Study equation is optimal for all populations and GFR ranges. Using a single equation for reporting requires a tradeoff to optimize performance at either higher or lower GFR ranges. A general practice and public health perspective favors the CKD-EPI equation.Kidney Disease: Improving Global Outcomes.

No study has compared cystatin C level, serum creatinine concentration, and estimated glomerular filtration rate (GFR) as risk factors for outcomes in chronic kidney disease (CKD), and none has compared measured GFR with CKD in any population.To compare cystatin C level with serum creatinine concentration and iothalamate GFR as risk factors for death and kidney failure.Observational study using serum cystatin C assayed from baseline samples of the Modification of Diet in Renal Disease Study (1989-1993).15 clinical centers in the United States that participated in the Modification of Diet in Renal Disease Study.825 trial participants with stage 3 or 4 nondiabetic CKD who had measurements of serum cystatin C.All-cause mortality, cardiovascular (CVD) mortality, and kidney failure until December 2000.Mean cystatin C level, creatinine concentration, and GFR were 2.2 mg/L (SD, 0.7), 212.16 micromol/L (SD, 88.4) (2.4 mg/dL [SD, 1.0]), and 33 mL/min per 1.73 m2 (SD, 12), respectively. Median follow-up was 10 years. Twenty-five percent of patients (n = 203) died of any cause, 15% (n = 123) died of CVD, and 66% (n = 548) reached kidney failure. In multivariate-adjusted models, 1-SD decreases in 1/creatinine, GFR, and 1/cystatin C were associated with increased risks for all-cause mortality of 1.27 (95% CI, 1.06 to 1.49), 1.27 (CI, 1.08 to 1.49), and 1.41 (CI, 1.18 to 1.67), respectively. For CVD mortality, the increased risks were 1.32 (CI, 1.05 to 1.64), 1.28 (CI, 1.04 to 1.59), and 1.64 (CI, 1.28 to 2.08), respectively. For kidney failure, the increased risks were 2.81 (CI, 2.48 to 3.18), 2.41 (CI, 2.15 to 2.70), and 2.36 (CI, 2.10 to 2.66), respectively.The Modification of Diet in Renal Disease Study cohort may not be representative of all patients with nondiabetic CKD because participants were more likely to reach kidney failure than death in follow-up.The association of cystatin C level with all-cause and CVD mortality was as strong as or perhaps stronger than that of iothalamate GFR with these outcomes in stage 3 or 4 CKD.

Background The influence of type of dialysis on survival of patients with end-stage renal disease (ESRD) is controversial. Objective To compare risk for death among patients with ESRD who receive peritoneal dialysis or hemodialysis. Design Prospective cohort study. Setting 81 dialysis clinics in 19 U.S. states. Patients 1041 patients starting dialysis (274 patients receiving peritoneal dialysis and 767 patients receiving hemodialysis) at baseline. Measurements Patients were followed for up to 7 years and censored at transplantation or loss to follow-up. Cox proportional hazards regression stratified by clinic was used to compare the risk for death with peritoneal dialysis versus hemodialysis. Results Twenty-five percent of patients undergoing peritoneal dialysis and 5% of hemodialysis patients switched type of dialysis. After adjustment, the risk for death did not differ between patients undergoing peritoneal dialysis and those undergoing hemodialysis during the first year (relative hazard, 1.39 [95% CI, 0.64 to 3.06]), but the risk became significantly higher among those undergoing peritoneal dialysis in the second year (relative hazard, 2.34 [CI, 1.19 to 4.59]). After stratification, the survival rate was no different for patients who had the highest propensity of being initially treated with peritoneal dialysis. Results were consistent with adjustment based on a propensity score model and in sensitivity analyses that used as-treated models and models in which switches in type of dialysis were treated as treatment failures. Results were similar but stronger in analyses that were restricted to patients who were treated only in clinics offering both types of dialysis. Limitations Patients were not randomly assigned to their initial type of dialysis. Also, more patients undergoing peritoneal dialysis than hemodialysis switched type of dialysis over time, and the reason for switching was often a consequence of the technique. Conclusions The risk for death in patients with ESRD undergoing dialysis depends on dialysis type. Further studies are needed to evaluate a possible survival benefit of a timely change from peritoneal dialysis to hemodialysis.

Hypertension is a risk factor for progression of chronic kidney disease. The optimal blood pressure to slow progression is unknown.To evaluate the effects of a low target blood pressure on kidney failure and all-cause mortality.Long-term follow-up of the Modification of Diet in Renal Disease Study, a randomized, controlled trial conducted from 1989 to 1993.15 outpatient nephrology practices.840 persons with predominantly nondiabetic kidney disease and a glomerular filtration rate of 13 to 55 mL/min per 1.73 m2.A low target blood pressure (mean arterial pressure92 mm Hg) or a usual target blood pressure (mean arterial pressure107 mm Hg).After the randomized trial was completed, kidney failure (defined as initiation of dialysis or kidney transplantation) and a composite outcome of kidney failure or all-cause mortality were ascertained through 31 December 2000.Kidney failure occurred in 554 participants (66%), and the composite outcome occurred in 624 participants (74%). After Cox proportional hazards modeling and intention-to-treat analysis, the adjusted hazard ratios were 0.68 (95% CI, 0.57 to 0.82; P0.001) for kidney failure and 0.77 (CI, 0.65 to 0.91; P = 0.0024) for the composite outcome in the low target blood pressure group compared with the usual target blood pressure group. Evidence was insufficient to conclude that the benefit of a low target blood pressure differed according to the cause of kidney disease, baseline glomerular filtration rate, or degree of proteinuria.The exact mechanism underlying the benefit of a low target blood pressure is unknown.Assignment to a low target blood pressure slowed the progression of nondiabetic kidney disease in patients with a moderately to severely decreased glomerular filtration rate.

Care for chronic renal failure involves management of complications and preparation for possible dialysis. Patients often are not evaluated by nephrologists in a timely manner.To identify factors associated with late evaluation by a nephrologist and to assess whether late evaluation is associated with worse survival once patients develop end-stage renal disease (ESRD).National prospective cohort study.81 dialysis facilities throughout the United States.828 patients with new-onset ESRD.Time from first evaluation by a nephrologist to initiation of dialysis, classified as late (4 months), intermediate (4 to 12 months), or early (12 months); rate of death, from initiation of dialysis to an average of 2.2 years of follow-up; and demographic, clinical, and laboratory characteristics.After adjustment for potential confounders, late evaluation was more common among black men than white men (44.8% vs. 24.5%; P0.05), uninsured patients than insured patients (56.7% vs. 29.0%; P0.05) and patients with severe comorbid disease than those with mild comorbid disease (35.0% vs. 23.0%; P0.05). Compared with patients who had early evaluation, the risk for death was greater among patients evaluated late and was graded (hazard ratio, 1.3 [95% CI, 0.87 to 2.06] for patients with intermediate evaluation and 1.8 [CI, 1.21 to 2.61] for those with late evaluation) after adjustment for dialysis method, demographic characteristics, and socioeconomic status in Cox proportional hazards regression analysis. After additional adjustment for such factors as the presence and severity of comorbid conditions, the association remained graded (hazard ratio, 1.2 [CI, 0.73 to 1.82] for patients evaluated at an intermediate point and 1.6 [CI, 1.04 to 2.39] for those evaluated late).Late evaluation of patients with chronic renal failure by a nephrologist is associated with greater burden and severity of comorbid disease, black ethnicity, lack of health insurance, and shorter duration of survival.

Chronic renal insufficiency leads to muscle wasting, which may be exacerbated by low-protein diets prescribed to delay disease progression. Resistance training increases protein utilization and muscle mass.To determine the efficacy of resistance training in improving protein utilization and muscle mass in patients with chronic renal insufficiency treated with a low-protein diet.Randomized, controlled trial.Tufts University, Boston, Massachusetts.26 older patients with moderate renal insufficiency (17 men, 9 women) who had achieved stabilization on a low-protein diet.During a run-in period of 2 to 8 weeks, patients were instructed and their adherence to the low-protein diet (0.6 g/kg of body weight per day) was evaluated. They were randomly assigned to a low-protein diet plus resistance training (n = 14) or a low-protein diet alone (n = 12) for 12 weeks.Total body potassium, mid-thigh muscle area, type I and II muscle-fiber cross-sectional area, and protein turnover.Mean protein intake was 0.64 +/- 0.07 g/kg per day after stabilization. Total body potassium and type I and II muscle-fiber cross-sectional areas increased in patients who performed resistance training by a mean (+/-SD) of 4% +/- 8%, 24% +/- 31%, and 22% +/- 29%, respectively, compared with those who did not. Leucine oxidation and serum prealbumin levels also improved significantly. Patients assigned to resistance training maintained body weight compared with those who were not. Improvement in muscle strength was significantly greater with resistance training (32% +/- 14%) than without (-13% +/- 20%) (P0.001).By improving muscle mass, nutritional status, and function, resistance training seems to be effective against the catabolism of a low-protein diet and uremia in patients with renal failure.

Background Patients with chronic kidney disease (CKD) are at increased risk for kidney failure, cardiovascular events, and all-cause mortality. Accurate models are needed to predict the individual risk for these outcomes. Purpose To systematically review risk prediction models for kidney failure, cardiovascular events, and death in patients with CKD. Data sources MEDLINE search of English-language articles published from 1966 to November 2012. Study selection Cohort studies that examined adults with any stage of CKD who were not receiving dialysis and had not had a transplant; had at least 1 year of follow-up; and reported on a model that predicted the risk for kidney failure, cardiovascular events, or all-cause mortality. Data extraction Reviewers extracted data on study design, population characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness. Data synthesis Thirteen studies describing 23 models were found. Eight studies (11 models) involved kidney failure, 5 studies (6 models) involved all-cause mortality, and 3 studies (6 models) involved cardiovascular events. Measures of estimated glomerular filtration rate or serum creatinine level were included in 10 studies (17 models), and measures of proteinuria were included in 9 studies (15 models). Only 2 studies (4 models) met the criteria for clinical usefulness, of which 1 study (3 models) presented reclassification indices with clinically useful risk categories. Limitation A validated risk-of-bias tool and comparisons of the performance of different models in the same validation population were lacking. Conclusion Accurate, externally validated models for predicting risk for kidney failure in patients with CKD are available and ready for clinical testing. Further development of models for cardiovascular events and all-cause mortality is needed. Primary funding source None.

Background : Dietary protein has long been thought to play a role in the progression of chronic renal disease, but clinical trials to date have not consistently shown that dietary protein restriction is beneficial. Purpose : To use meta-analysis to assess the efficacy of dietary protein restriction in previously published studies of diabetic and nondiabetic renal diseases, including the recently completed Modification of Diet in Renal Disease Study. Data Sources : The English-language medical literature published from January 1966 through December 1994 was searched for studies examining the effect of low-protein diets in humans with chronic renal disease. A total of 1413 patients in five studies of nondiabetic renal disease (mean length of follow-up, 18 to 36 months) and 108 patients in five studies of type I diabetes mellitus (mean length of follow-up, 9 to 35 months) were included. Study Selection : Randomized, controlled studies were selected for nondiabetic renal disease ; randomized, controlled studies or time-controlled studies with nonrandomized crossover design were selected for diabetic nephropathy. Data Extraction : Data in tables, figures, or text were independently extracted by two of the authors. Data Synthesis : The relative risk for progression of renal disease in patients receiving a low-protein diet compared with patients receiving a usual-protein diet was calculated by using a random-effects model. In five studies of nondiabetic renal disease, a low-protein diet significantly reduced the risk for renal failure or death (relative risk, 0.67 [95% CI, 0.50 to 0.89]). In five studies of insulin-dependent diabetes mellitus, a low-protein diet significantly slowed the increase in urinary albumin level or the decline in glomerular filtration rate or creatinine clearance (relative risk, 0.56 [Cl, 0.40 to 0.77]). Tests for heterogeneity showed no significant differences in relative risk among studies of either diabetic or nondiabetic renal disease. No significant differences were seen between diet groups in pooled mean arterial blood pressure (diabetic and nondiabetic patients) or glycosylated hemoglobin level (diabetic patients only). Conclusion : Dietary protein restriction effectively slows the progression of both diabetic and nondiabetic renal diseases.

In this issue, Tonelli and colleagues compared a new classification for patients with CKD that incorporates eGFR and proteinuria with the current system that considers only eGFR. The editorialists ...

Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values.To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates.Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006.8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES.GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age.In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%).The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR.The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.National Institute of Diabetes and Digestive and Kidney Diseases.

In this issue, Rahman and colleagues report cardiovascular disease in chronic kidney disease from the randomized study known as ALLHAT. They had previously reported outcomes of kidney disease in th...

Several recent studies have tried to characterize the effects of a lower-than-usual target blood pressure on progression of nondiabetic kidney disease. An observational study, the Modification of D...

Estimating equations that accurately calculate glomerular filtration rate (GFR) in patients with chronic kidney disease and normal renal function are potentially important for early detection of di...

Background: Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and urine protein excretion and slow the progression of chronic kidney disease. Purpose: To determine the levels of blood pressure and urine protein excretion associated with the lowest risk for progression of chronic kidney disease during anti hypertensive therapy with and without ACE inhibitors. Data Sources: 11 randomized, controlled trials comparing the efficacy of anti hypertensive regimens with or without ACE inhibitors for patients with predominantly nondiabetic kidney disease. Study Selection: MEDLINE database search for English-language studies published between 1977 and 1999. Data Extraction: Data on 1860 nondiabetic patients were pooled in a patient-level meta-analysis. Progression of kidney disease was defined as a doubling of baseline serum creatinine level or onset of kidney failure. Multivariable regression analysis was performed to assess the association of systolic and diastolic blood pressure and urine protein excretion with kidney disease progression at 22610 patient visits. Data Synthesis: Mean duration of follow-up was 2.2 years. Kidney disease progression was documented in 311 patients. Systolic blood pressure of 110 to 129 mm Hg and urine protein excretion less than 2.0 g/d were associated with the lowest risk for kidney disease progression. Angiotensin-converting enzyme inhibitors remained beneficial after adjustment for blood pressure and urine protein excretion (relative risk, 0.67 [95% CI, 0.53 to 0.84]). The increased risk for kidney progression at higher systolic blood pressure levels was greater in patients with urine protein excretion greater than 1.0 g/d (P Conclusion: Although reverse causation cannot be excluded with certainty, a systolic blood pressure goal between 110 and 129 mm Hg may be beneficial in patients with urine protein excretion greater than 1.0 g/d. Systolic blood pressure less than 110 mm Hg may be associated with a higher risk for kidney disease progression.

Background: The effect of angiotensin-converting enzyme (ACE) inhibitors in slowing the decline in renal function in nondiabetic renal disease varies among studies. Purpose: To use meta-analysis to...

The serum creatinine concentration is widely used as an index of renal function, but this measure is affected by factors other than the glomerular filtration rate (GFR). This study examined an equa...

Background The effect of angiotensin-converting enzyme (ACE) inhibitors in slowing the decline in renal function in nondiabetic renal disease varies among studies. Purpose To use meta-analysis to assess the effect of ACE inhibitors on the development of end-stage renal disease caused by factors other than diabetes. Data sources The English-language medical literature, identified by a MEDLINE search and unpublished studies. Study selection All randomized studies that compared ACE inhibitors with other antihypertensive agents and had at least 1 year of planned follow-up were selected. Studies of diabetic renal disease and renal transplants were excluded. A total of 1594 patients in 10 studies was included. Data extraction Data on end-stage renal disease, death, drop out, and blood pressure were extracted. Study investigators confirmed results and provided additional data. Data synthesis Among 806 patients receiving ACE inhibitors, 52 (6.4%) developed end-stage renal disease and 17 (2.1%) died; in the 788 controls, the respective values were 72 (9.1%) and 12 (1.5%). The pooled relative risks were 0.70 (95% CI, 0.51 to 0.97) for end-stage renal disease and 1.24 (CI, 0.55 to 2.83) for death; the studies were not significantly heterogeneous. The decreases in weighted mean systolic and diastolic blood pressures during follow-up were 4.9 and 1.2 mm Hg greater, respectively, in the patients who received ACE inhibitors. Conclusions Angiotensin-converting enzyme inhibitors are more effective than other antihypertensive agents in reducing the development of end-stage nondiabetic renal disease, and they do not increase mortality. It could not be determined whether this beneficial effect is due to the greater decline in blood pressure or to other effects of ACE inhibition.

Objective To describe the clinical course of severe lupus nephritis and to identify the risk factors for progression to renal failure among patients treated with prednisone and short-term courses of low-dose oral cyclophosphamide. Design Ancillary analyses of data from the Lupus Nephritis Collaborative Study (LNCS). Setting University hospital medical centers (14). Patients The 86 patients who participated in the LNCS (mean follow-up, 136 weeks [2.6 years]) and a subgroup of 63 patients with follow-up of more than 48 weeks (mean follow-up, 160 weeks [3.1 years]). Measurements Initial clinical and pathologic features, response to therapy within 48 weeks, and subsequent clinical events, including development of renal failure. Main results Renal failure developed in 18 patients (21%). An observed elevation in serum creatinine concentration was the only initial feature predictive of subsequent renal failure. Mean (+/- SD) initial serum creatinine levels were higher in patients who subsequently developed renal failure (244 +/- 134 mumol/L [2.76 +/- 1.52 mg/dL] compared with 163 +/- 103 mumol/L [1.85 +/- 1.17 mg/dL]; P = 0.007). The risk for renal failure was higher among patients with initial serum creatinine levels greater than 106 mumol/L (1.2 mg/dL) (29% compared with 6.5%; P = 0.014). Response to therapy (defined as resolution of initial serum creatinine elevations within 48 weeks) refined the prognosis based on initial serum creatinine determinations. The risk for subsequent renal failure was higher among patients who failed to respond to therapy within 48 weeks (30% compared with 0%; P = 0.015). By comparison, 9% of patients with normal initial serum creatinine levels progressed to renal failure after 48 weeks. Conclusions Initial serum creatinine levels and responses to initial therapy with prednisone and short-term cyclophosphamide, as used in the LNCS, can guide further therapy. Patients with normal initial serum creatinine levels or resolution of initial serum creatinine elevations within 48 weeks have a low risk for renal failure and may not require long-term treatment with cyclophosphamide.

We used decision analysis to compare the conventional strategy of biopsy-tailored therapy with alternative strategies not using renal biopsy in treating adults with idiopathic nephrotic syndrome. We evaluated data on steroid and platelet-inhibitor therapies and a new clinical strategy, empiric sequential therapy. This sequential approach involves use of short-term alternate-day steroid agents, followed by long-term platelet inhibitors for persistent nephrotic syndrome. Our results indicate that, contrary to usual practice, use of renal biopsy is not necessary in caring for adult patients with idiopathic nephrotic syndrome; empiric short-term alternate-day steroid therapy is equally efficacious. If the benefits of platelet-inhibitor therapy for treating membranoproliferative glomerulonephritis are confirmed, empiric sequential therapy also will be equally efficacious. Our study shows how decision analysis can be used to identify superfluous diagnostic procedures.