The prognosis of severe lupus nephritis based on the Modification of Diet in Renal Disease (MDRD) study estimated glomerular filtration rate.

The level of renal function at biopsy is predictive of outcome in patients with severe lupus nephritis (SLN). While renal function has been based on serum creatinine (SCr) alone, measuring the estimated glomerular filtration rate (eGFR) utilizing the Modification of Diet in Renal Disease (MDRD) Study equation has been found to be more accurate. The MDRD eGFR (ml/min/1.73 m(2)) at biopsy was calculated in 86 patients with SLN and patients were categorized based on eGFR: ≥60 (33 pts), 59-30 (33 pts) and <30 (20 pts). An eGFR was <60 in 18% of patients with a normal SCr. After 120 ± 65 months of follow-up, attainment of a complete remission (76% versus 30% versus 10%, p < 0.0001) and patient survival without end-stage renal disease (ESRD; 10 year survival: 85% versus 45% versus 14%, p < 0.0001 overall) was highest in patients with an eGFR ≥60 and lowest in those with an eGFR <30. The long-term prognosis for patients with severe lupus nephritis and an eGFR ≥60 was extremely good. Since the prognosis for patients with an eGFR <60 was poor even in those patients with a normal SCr, renal function is more accurately determined by the MDRD eGFR.

Evidence of concurrent immunopathological mechanisms determining the pathology of severe lupus nephritis.

The purpose of this study is to determine whether two distinct histopathological-immunopathological lesions, which have been reported in severe lupus nephritis, diffuse global glomerulonephritis (GN) (WHO IV) and a segmental and necrotising GN (WHO III) can be reported to coexist in a single patient. We examine the evidence of coexistence of these disparate lesions and the prognostic significance in a group of patients with severe lupus nephritis who have been subjected to a common therapeutic regimen by protocol. The simple, reproducible parameter indicating the presence of glomerular capillary necrosis was the presence of crescents. We, therefore, reviewed 39 renal biopsies with diffuse global lupus GN (WHO IV) (Churg, J, Sobin, LH. Lupus nephritis. Renal disease, classification and atlas of glomerular diseases. New York: Igaku-Shoin; 1982. p. 127-149). and used crescents as a surrogate for glomerular necrosis. Peripheral capillary immune deposits were less prominent in WHO IV with crescents compared with those without and resembled the reduced immune deposits seen in severe segmental GN (WHO III >or= 50%). Patients with WHO IV with crescents had decreased survival without end-stage renal disease (P = 0.02), fewer remissions (P = 0.04) and more adverse outcomes (12/22 vs 3/17) (P = 0.02) than those without crescents, and this was similar to patients with WHO III >or=50%. We conclude that, on the basis of immunological and morphological features, WHO IV with crescents appears to be the result of two distinct pathogenetic mechanisms. We propose that diffuse global lupus GN, associated with crescents, is best described as WHO class IV + WHO class III.

Severe lupus nephritis: importance of re-evaluating the histologic classification and the approach to patient care.

The histopathology of severe lupus glomerulonephritis comprises distinct patterns of injury which were initially defined by the World Health Organization Classification of 1982 as focal and segmental glomerulonephritis (category III), diffuse proliferative glomerulonephritis (category IV) and complex membranous glomerulonephritis (categories Vc, Vd). It is assumed that the morphologic abnormalities demonstrated in this classification represent distinctive differences in the mediation of the immune response which leads to a specific type of glomerular inflammation. In 1995 the World Health Organizational committee recommended a change in categorization of focal and segmental glomerulonephritis (class III) and diffuse proliferative glomerulonephritis (class IV), which would overlook the morphological differences between these categories and treat them as a continuum, recommending that biopsies classified as focal and segmental glomerulonephritis (category III) with involvement of > or =50% of glomeruli be included into the diffuse proliferative glomerulonephritis category (category IV). Since the classification of severe lupus nephritis has significant impact on prognosis and the therapeutic approach to patients with this disease, it is the purpose of this review to critically re-examine the existing classification based on new insights into differences in morphologic features and long-term outcome.

Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis.

BACKGROUND: Patients with systemic lupus erythematosus have a spectrum of glomerular disease, but the different patterns of glomerular injury identified within the general category of "severe" lupus glomerulonephritis are responsible for much of the morbidity and mortality in this disease. The glomerular injury patterns seen with severe lupus glomerulonephritis have been separated into distinct histopathologic groups to determine whether they can predict long-term patient outcome. METHODS: We analyzed the clinical follow-up of 85 patients participating in a controlled prospective therapeutic trial for the treatment of severe lupus glomerulonephritis conducted from April 1981 to December 1988, with an average follow-up of 10 years. Patients were classified according to the 1982 World Health Organization classification for lupus glomerulonephritis. RESULTS: During the course of follow-up [120 +/- 65 (SD) months], 60% of patients with category IV (diffuse proliferative glomerulonephritis) lesions entered a remission compared with only 38% of patients with category III (> or =50%, focal and segmental glomerulonephritis) lesions and 27% of patients with category Vc (> or =50%) and Vd (P < 0.05). Renal survival at 10 years was 75% for those with category IV lesions, 47% for patients with category Vc (> or =50%) and Vd, and 52% for patients with category III (> or =50%) lesions (P < 0.05). Based on multivariate analysis, patients with category III (> or =50%) or Vc (> or =50%) and Vd lesions had a relative risk of progression to end-stage renal disease 2.9 times that of category IV patients (P < 0.01), while the likelihood of entering a remission was 8.2 times greater for category IV patients (P = 0.0001). CONCLUSION: The histopathologic categorization among patients with severe lupus glomerulonephritis provides information relevant to their long-term outcome.

The treatment of primary focal segmental glomerulosclerosis.

Nephrotic patients with primary focal segmental glomerulosclerosis (FSGS) have a poor prognosis with 50% progressing to end stage renal disease (ESRD) over 3 to 8 years. The achievement of a remission in proteinuria has been associated with a significantly improved renal survival as compared to those patients not attaining a remission. Unfortunately, spontaneous remissions are rare in FSGS, and the response to therapy has historically been poor. Recent experience with more aggressive immunosuppressive therapy has lead to an increase in the remission rate for FSGS patients and given rise to optimism in the treatment of this glomerulopathy.

Patient survival among incident peritoneal dialysis and hemodialysis patients in an urban setting.

We retrospectively evaluated 432 patients (336 black; 78%; and 96 white; 22%) incident to our peritoneal dialysis (PD; 195 patients; 45%) and hemodialysis (HD; 237 patients; 55%) programs from January 1987 to December 1997 who survived their first 90 days of dialysis therapy. Black patients comprised 70% of the PD and 84% of the HD patients (P: < 0.01). PD patients were more often men and younger than HD patients and less often had diabetes (40% versus 56% of HD patients; P: < 0.01) and cardiac disease (44% versus 58% of HD patients; P: < 0.01) than HD patients. Adjusting for baseline clinical and comorbid features, patient survival was determined by Cox regression analysis. Survival was better on PD therapy overall (relative risk [RR] for PD versus HD, 0.80; 1-, 2-, and 5-year survival rates, 90%, 77%, and 43% on PD versus 88%, 72%, and 35% on HD, respectively; P: = 0.21) and among black patients (RR for PD versus HD, 0.69; 1-, 2-, and 5-year survival rates, 92%, 80%, and 52% on PD versus 88%, 74%, and 40% on HD, respectively; P: = 0.09), but these were not statistically significant. The RR for PD versus HD was 1.08 for white patients (1-, 2-, and 5-year survival rates, 82%, 61%, and 23% for PD versus 82%, 62%, and 24% for HD; P: = 0.79). Significant predictors of mortality were race (RR for whites versus blacks, 1.51), age (RR, 1.03), cardiac disease (RR, 1.57), baseline albumin level (RR, 0.60), baseline serum creatinine level (RR, 0.91), baseline blood urea nitrogen level (RR, 1.01), and baseline weight (RR, 0.98). In conclusion, patient survival on dialysis therapy is significantly better for black patients and for patients entering dialysis with signs of adequate nutrition (increased weight and creatinine and albumin levels) and without evidence of cardiac disease. In an urban dialysis program, we find that adjusted patient survival on PD equals or is better than that on HD therapy, particularly among black patients, making PD a viable alternative to HD in our patient population.

Polymicrobial peritonitis in continuous ambulatory peritoneal dialysis patients.

We retrospectively evaluated 232 continuous ambulatory peritoneal dialysis (CAPD) patients entering our program from January 1, 1987, to December 31, 1997, for polymicrobial peritonitis. Polymicrobial peritonitis occurred in 16% of the patients (polymicrobial-peritonitis group), whereas 52% of the patients had peritonitis episodes with only a single organism (single-organism group), and 32% of the patients had no episode of peritonitis. Polymicrobial peritonitis accounted for 8% of the 554 peritonitis episodes, occurred after 23 +/- 20 months on peritoneal dialysis (PD), and was preceded by greater than three episodes of peritonitis in 73% of the patients. Peritonitis rates were greater in the polymicrobial-peritonitis group compared with patients in the single-organism group (1.8 versus 1.2 episodes/patient-year; P: < 0.001). The majority of polymicrobial infections involved gram-negative and/or fungal pathogens, but in 21% of the episodes, only gram-positive organisms were identified. An intra-abdominal process was identified in only 7% of the patients. Catheter loss overall was greatest in the polymicrobial-peritonitis group (65% versus single-organism group, 30% versus patients without peritonitis, 5%; P < 0.001), but only 33% of the polymicrobial infections resulted in catheter loss. At last follow-up, 70% of the patients in the polymicrobial-peritonitis group had permanently transferred to hemodialysis compared with 25% from the single-organism group and 15% from the no-peritonitis group (P < 0.001). In conclusion, polymicrobial peritonitis is an infrequent but serious complication of CAPD that occurs late in the course of PD and is often preceded by recurrent episodes of peritonitis. Polymicrobial peritonitis is rarely the result of a catastrophic intra-abdominal process, and although the majority of patients can be successfully treated without catheter removal, the long-term prognosis is poor, with a high rate of transfer to hemodialysis.

Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group.

In 1992, we published the results of a prospective, controlled trial of aggressive therapy (high-dose prednisone plus oral cyclophosphamide alone or with plasmapheresis) in 86 patients with severe lupus nephritis. During this study, remission (serum creatinine < or =1.4 mg/dL [< or =123 micromol/L] and proteinuria < or =330 mg/d of protein) in renal disease occurred in 37 patients (43%). To assess the long-term effect of remission on patient and renal survival, we now report the results of our extended follow-up of these patients. After an average of 10 years of follow-up in the 86 patients, patient survival rates at both 5 and 10 years were 95% in the group that had a remission and 69% at 5 years and 60% at 10 years in the no-remission group (P < 0.001). Renal survival rates were 94% at both 5 and 10 years in the remission group compared with 46% at 5 years and 31% at 10 years in the no-remission group (P < 0. 0001). Features predictive of remission included stable renal function after 4 weeks on therapy, category IV lesion, lower chronicity index, white race, lower urine protein excretion level at baseline, and lower baseline serum creatinine level. The features predictive of end-stage renal disease were higher baseline serum creatinine level, presence of anti-Ro antibodies, and failure to attain a remission. Thus, in patients with the most severe forms of lupus nephritis, a remission of clinical renal abnormalities is associated with dramatic improvement in long-term patient and renal survival.

Von Hippel-Lindau disease with multiple malignant renal tumors: the importance of genetic testing.

We present an adult man who, while being evaluated for gross hematuria, was found to have polycystic kidneys and multiple bilateral renal cell carcinomas. Further evaluation and the presence of a significant family history of cancer suggested the diagnosis of von Hippel-Lindau disease. Through the aid of genetic testing, this unusual diagnosis was confirmed and led to the identification of other family members with the von Hippel-Lindau gene. Patients with von Hippel-Lindau disease have an increased incidence of malignant carcinomas and the syndrome can mimic the presentation of other cystic diseases of the kidney. Early diagnosis and genetic screening of family members is essential to improve the prognosis and survival of those affected.

A multicenter study of noncompliance with continuous ambulatory peritoneal dialysis exchanges in US and Canadian patients.

Recent evidence suggested that noncompliance (NC) with continuous ambulatory peritoneal dialysis (CAPD) exchanges may be more common in US than in Canadian dialysis centers. This issue was investigated using a questionnaire-based method in 656 CAPD patients at 14 centers in the United States and Canada. NC was defined as missing more than one exchange per week or more than two exchanges per month. Patients were ensured of the confidentiality of their individual results. Mean patient age was 56 +/- 16 years, 52% were women, and 39% had diabetes. The overall admitted rate of NC was 13%, with a rate of 18% in the United States and 7% in Canada (P < 0.001). NC was more common in younger patients (P < 0.0001), those without diabetes (P < 0.001), and employed patients (P < 0.05). It was also more common in black and Hispanic than in Asian and white patients (P < 0.001). NC was more common in patients prescribed more than four exchanges daily (P < 0.0001) but was not affected by dwell volume. On multiple regression analysis, the independent predictors of NC, in order of importance, were being prescribed more than four exchanges per day, black race, being employed, younger age, and not having diabetes. Being treated in a US unit did not quite achieve significance as a multivariate independent predictor. These findings suggest that NC is not uncommon in CAPD patients and is more frequent in US than in Canadian patients. However, country of residence is less powerful as a predictor of NC than a variety of other demographic and prescription factors.

Long-term Outcome of Adult Onset Idiopathic Minimal Change Disease.

Minimal Change Disease (MCD) is the lesion most commonly associated with nephrotic syndrome in children, accounting for over 75% of cases. Although less common, MCD still accounts for up to 30% of adult onset nephrotic syndrome. Unlike children, in whom MCD is primarily idiopathic, secondary causes of MCD are seen in 13% of adults and must be considered, as the therapeutic approach to these patients is defined by the underlying cause. Clinical features at presentation in nephrotic adults with MCD can include microscopic hematuria, hypertension, and renal insufficiency, making MCD indistinguishable clinically from focal segmental glomerulosclerosis. As a result, a renal biopsy is required in adults in order to correctly diagnose and manage the nephrotic syndrome. As in children, response to therapy leads to a complete remission of proteinuria in up to 97% of adults, although, adults require a more prolonged course of therapy (16-28 weeks) compared to children (8 weeks). Relapse of MCD is extremely common in children (71%) and can be seen in up to 85% of adult patients. Relapses occur more frequently in younger adults (< 45 years) and are often seen in the first 6-12 months after the onset of a remission. Successful treatment of relapses can often be achieved with a second course of steroids. However, up to 50% of relapsing adults become frequent relapsers or steroid dependent. In these patients, a stable remission can be induced by treatment with either cyclophosphamide or cyclosporine. Overall, the long-term outcome of adult onset MCD is excellent, with fewer than 5% of patients progressing to end-stage renal disease and a patient survival of 83%-98% at 15 years.

Racial differences in survival in an urban peritoneal dialysis program.

We retrospectively evaluated 233 incident patients (61% black, 27% white, and 12% Hispanic/Asian) to our peritoneal dialysis (PD) program from January 1987 to September 1997 to identify any possible racial differences in patient survival. Information collected included clinical features, comorbid conditions, nutritional status, and dialysis dose at initiation of dialysis. The average age was 52 +/- 16 (SD) years, and 49% were men. Diabetes mellitus was present in 41% of patients. Overall follow-up was 31 +/- 24 (median 26) months during which time 21% of patients underwent transplant, 29% of patients transferred to hemodialysis (HD), and 42% of patients died. The Cox proportional hazards analysis, based on intent-to-treat, identified age (RR: 1.03), race (RR: 2.35, white versus black), cardiac disease (RR: 1.97), and serum albumin (RR: 0. 44) to independently predict mortality. Further analysis was performed based on diabetic status, and the analysis identified age (RR: 1.06), race (RR: 2.45, white versus black), and peripheral vascular disease (RR: 2.88) as predictors of mortality in diabetic patients. In nondiabetic patients, age (RR: 1.03), race (RR: 2.24, white versus black), cardiac disease (RR: 2.48), cerebrovascular disease (RR: 3.17), and serum albumin (RR: 0.39) were significant predictors of mortality. The significance of race persisted even after adjusting patients transferring to hemodialysis. The adjusted patient survival at 1, 2, and 5 years was 94%, 87% and 53% for black patients, and 86%, 72%, and 23% for white patients. The adjusted patient survival in diabetics at 1, 2, and 5 years was 92%, 79%, and 37% for black patients, and 82%, 56%, and 9% for white patients. The adjusted patient survival in nondiabetics at 1, 2, and 5 years was 94%, 91%, and 63% for black patients, and 88%, 82%, and 35% for white patients. In conclusion, long-term patient survival is better for black patients than white patients in our peritoneal dialysis program. Peritoneal dialysis should be considered a viable dialytic option for black patients entering an end-stage renal disease program.

Focal segmental glomerulosclerosis: prognostic implications of the cellular lesion.

The cellular lesion (CELL), seen in some patients with primary focal segmental glomerulosclerosis (FSGS), comprises proliferation, hypertrophy, and pathologic changes in the cells overlying the glomerular scar. The prognosis of the cellular lesion was retrospectively studied in 100 patients with FSGS (43 had FSGS-CELL and 57 had FSGS without the cellular lesion (classic segmental scar [CS]). Patients with the FSGS-CELL lesion were more often black and severely proteinuric and developed more end-stage renal disease (ESRD). Nephrotic patients with FSGS-CELL (n = 39) were more proteinuric at presentation than patients with FSGS-CS (n = 36). ESRD developed more frequently in patients with the FSGS-CELL (17 of 39, 44% versus 5 of 36, 14%, P = 0.005), and patients with extensive FSGS-CELL (> or = 20% glomeruli) were mainly black (94%), severely nephrotic (67%, >10 g/d), and had a poor response to treatment (23% remission). In nephrotic patients, initial serum creatinine, interstitial expansion > or = 20%, and CELL independently predicted ESRD. However, the rates of remission in treated nephrotic patients with FSGS-CELL and FSGS-CS were the same (9 of 17, 53% versus 17 of 39, 52%), and patients in both groups who achieved a remission had a 5-yr survival of 100%. Steroid treatment was the only variable that predicted remission. Patients with the FSGS-CELL have an increased prevalence of ESRD, but the improved prognosis associated with remission is so significant that a therapeutic trial is warranted in all nephrotic FSGS patients, regardless of the presence of the cellular lesion.

Sclerosing peritonitis and systemic lupus erythematosus: a report of two cases.

OBJECTIVE: To heighten the awareness of a possible association of sclerosing peritonitis in patients with systemic lupus erythematosus (SLE). METHODS AND RESULTS: Over the course of 17 years (from January 1981 to December 1997), 371 patients were treated with continuous ambulatory peritoneal dialysis (CAPD) at Rush-Presbyterian-St Lukes Medical Center. The patients were followed on CAPD for an average of 25 +/- 21 (SD) months with a median of 19 months (range 0.2-115 months). During this time only 2 (0.5%) patients were diagnosed with sclerosing peritonitis, and both had SLE with ongoing evidence of active disease while on CAPD. With a total of 26 SLE patients being treated with CAPD during the observation period, the prevalence of sclerosing peritonitis can be said to be as high as 8% in this patient population. CONCLUSION: These cases suggest that autoimmune diseases, such as SLE, that are well known to cause immune-mediated serositis may represent an additional factor predisposing to the development of sclerosing peritonitis in patients treated with CAPD.

Clinical picture and outcome of primary focal segmental glomerulosclerosis.

Patients with primary focal segmental glomerulosclerosis (FSGS) present with proteinuria (often the nephrotic syndrome), microscopic haematuria, hypertension and renal insufficiency. Overall, this glomerular lesion is seen in approximately 20% of nephrotic adults and children, but is observed much more commonly in the black than the white population (prevalence as high as 80%). Characteristically, nephrotic patients, particularly those with massive proteinuria, have a significantly poorer prognosis than non-nephrotic patients, with 50% progressing to end-stage renal disease (ESRD) over 3-8 years as compared with a 10-year survival of >80%, respectively. In addition, the recurrence rate of this lesion is high in transplanted patients with primary FSGS. When clinical and histological features at presentation have been evaluated by multivariate analysis, the significant positive predictors of progression to ESRD have consistently been the serum creatinine (>1.3 mg/dl), amount of proteinuria and the presence of interstitial fibrosis (> or =20%). The only factor found to be a significant negative predictor of progression to ESRD has been the achievement of a remission in proteinuria. Unfortunately, spontaneous remissions are rare in FSGS, occurring in < or =6% of patients. The factor identified as most associated with achieving a remission in nephrotic patients with primary FSGS has been treatment.

Evaluation of ultrafiltration failure.

The evaluation of ultrafiltration failure is embarked upon when a patient has persistent problems with symptoms and signs of fluid overload. Fluid overload is a common problem in peritoneal dialysis (PD) patients and the risk of its occurrence increases with time on dialysis. Although often attributed to changes in peritoneal membrane function (membrane failure), there are a number of potential, and frequently more common factors that can contribute to the failure of adequate fluid removal in patients on PD. Many of the causes of ultrafiltration failure may be apparent after an initial informal evaluation. However, if after this the etiology remains unexplained, a systematic approach to the differential diagnosis of this problem can be utilized with the use of the peritoneal equilibration test. Once a diagnosis is confirmed, a logical therapeutic plan can be formulated.