The clinical relevance of repeat renal biopsies in the management of lupus nephritis: a South African experience.

Purpose Clinically, repeat renal biopsies (RRBs) have been performed in lupus nephritis to identify changes in class, plan treatment and assist in prognostication. We set out to compare the histopathological features and outcomes of disease flare and protocol biopsy patients. Methods A retrospective descriptive study was conducted on repeat biopsies performed between January 1984 and December 2015 in lupus nephritis patients. Disease flares and protocol biopsies were compared. Results Of 614 systemic lupus erythematosus (SLE) renal biopsies, 127 (20.7%) RRBs were identified. Disease flare patients accounted for 96 (75.6%) and protocol biopsies for 31 (24.4%) of RRBs. Seventy (72.9%) disease flare patients retained their original class on repeat biopsy. When categorised as proliferative and non-proliferative histology, 83 (87.4%) of the disease flare biopsy patients remained histologically unchanged. Treatment remained unchanged in 57 (60.0%) patients following RRBs for disease flares. Response to immunosuppression in disease flare patients was poorer. Non-response was associated with increased chronicity index (OR = 1.33; 95% CI 1.01-1.76; p = 0.045). Thirty-three (36.3%) disease flare patients developed end-stage kidney disease (ESKD) in one year as compared to one (3.6%) protocol biopsy patient ( p = 0.003). ESKD in disease flare patients was associated with non-response to treatment (OR = 24.6; 95% CI 2.7-219.3; p = 0.004) on multivariate analysis. One-year mortality was 30.0% in the disease flare patients and 3.5% in protocol biopsy patients ( p = 0.018). Conclusion Repeat biopsies in disease flare patients infrequently led to histological class changes, failed to lead to change of treatment in the majority of patients, and were associated with poorer outcomes.

Lupus nephritis in the Western Cape, a high prevalence area: an experience over three decades.

Background Systemic lupus erythematosus is a multisystem disease with serious complications, including lupus nephritis. Systemic lupus erythematosus is prevalent in the Western Cape, predominantly affecting women in the prime of their lives. Renal biopsy is an important tool for the management of the lupus patient with kidney disease, guiding treatment and assessing prognosis. Aims The aim of this study was to ascertain if there has been a change in the spectrum of renal pathology, patient characteristics and long-term outcomes in patients with lupus nephritis in our region over three decades. Methods We reviewed 315 records of systemic lupus erythematosus patients with suspected renal disease who underwent renal biopsy in the Renal Unit at Tygerberg Hospital over three decades between January 1983 and December 2012. Results Lupus nephritis consistently affected young women. Class IV lupus nephritis remained the most common pattern throughout the three decades. The overall five-year survival for this cohort was 67% (95% confidence interval (CI), 60-72%). Conclusion Class IV lupus nephritis remained the most frequent class in our cohort of patients with the poorest survival rates compared to other classes. The prognosis of lupus nephritis in our region is considerably worse than that reported elsewhere in the world.

Acute tubulointerstitial nephritis related to antituberculous drug therapy.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) as a complication of antituberculous therapy has been most commonly reported due to rifampicin therapy. This reaction typically occurs following re-exposure to the drug. This study undertook to investigate the clinicopathological features of ATIN related to antituberculous therapy. METHODS: We performed a retrospective study of all adult patients with a biopsy-proven diagnosis of ATIN on chemotherapy for tuberculosis. The patients presented with acute renal failure at our institution during 1995 - 2007. The demographic, clinical, biochemical and histopathological features were studied. The patient outcome and management were analyzed. RESULTS: 41 patients had histologically proven ATIN. 23 (56%) were female. The mean age at presentation was 42 years. The most common regimen included rifampicin used intermittently to treat pulmonary tuberculosis. The average duration of antituberculosis therapy was 19 days before presentation and the duration of the acute illness averaged 5 days. The most common clinical manifestation included gastro-intestinal symptoms occurring in 35 (85%) patients with associated hepatitis biochemically in 20 (53%) patients. No skin rashes were observed and eosinophilia was only present in two patients. Hematuria was observed universally without any significant proteinuria. Anemia was present in 37 (90%) patients, with associated thrombocytopenia in 15 (37%). Rifampicin was discontinued in 37 (90%) cases. Nine (22%) patients required dialysis. One patient failed to recover renal function and 4 (10%) patients died. Mortality was related to overwhelming tuberculosis infection. The main factor predicting the need for dialysis was duration of oliguria. CONCLUSION: ATIN is a rare, but serious complication of repeat antituberculous therapy mainly due to re-exposure to rifampicin. Although the renal prognosis is generally good the disease does carry significant morbidity and mortality risks. A high index of suspicion is needed in re-treatment patients. A suggested screening test is for microhematuria with urine dipstix.

Lymphoproliferative disorders in Oxford renal transplant recipients.

BACKGROUND: Increased cancer incidence, particularly lymphoproliferative disease, is a complication of immunosuppression in organ transplantation. Non-Hodgkin's lymphomas (NHLs) occur frequently during the first year after transplantation, more so in North America than in Europe. METHODS: This study audited and correlated the demographic, clinical, pathological, and outcome features of post-transplant lymphoproliferative disorders (PTLDs) in a large centre in Oxford, and assessed whether the time of onset fitted more with the European or North American pattern. RESULTS: There were 1383 renal transplants in the study period and 27 patients developed lymphoma: 26 NHLs and one Hodgkin's disease (1.95%). Four of the patients never received cyclosporin. The mean time of diagnosis after transplant was 46 months. Most tumours (21/27) presented extranodally. Management included reduction of immunosuppression, surgical excision, antiviral treatment, radiotherapy, and chemotherapy. Three patients presented in the first post-transplant year-0.34% of cyclosporin managed patients-similar to the North American incidence, although the incidence of extranodal late PTLDs was also high (mean onset, 36 months v 15 months international mean). Post-transplant lymphomas were the most common malignancy associated with death in transplant patients. CONCLUSIONS: PTLDs occurred in 2% of renal transplant patients, presenting both in the first year in association with cyclosporin use, as in North America, but also in subsequent years, giving an overall presentation time later than the international mean. The disease usually presented extranodally, accounting for the wide range of symptoms and signs. Despite awareness and active management, the disease contributed to death in more that 50% of patients with PTLDs.

Subtypes of acute postinfectious glomerulonephritis: a clinico-pathological correlation.

The case records and histopathology of 42 adults with the characteristic light and electron microscopic features of Acute Postinfectious Glomerulonephritis (APGN) were studied. The biopsies were divided into three subtypes depending on the form and distribution of subepithelial "humps" and other immune-complex deposits on electron microscopy (EM): the "starry sky", "garland" and "mesangial" patterns. There was no significant difference between the three subtypes with regard to age, hypertension, creatinine, anti-streptolysin 0 titer and low serum complement levels on presentation. The "garland" subtype had significantly more proteinuria than both the "starry sky" (p = 0.04) and "mesangial" (p = 0.003) subtypes. The "mesangial" pattern had a lesser degree of cellular proliferation and leukocytosis in the glomeruli than the other subtypes. The "starry sky" subtype was present in 4 of the 5 cases of crescentic nephritis and in 6 of the 7 patients with a chronic course. Our study suggests that the higher degree of proteinuria in the "garland" subtype and the chronic course of the "starry sky" subtype are the main clinical features that distinguish the three histological subtypes. Our patients, from a developing community with poor socio-economic conditions, had a poor prognosis.

Pregnancy in partially remitted hepatitis B-associated membranous glomerulonephritis.

Hepatitis B-associated glomerulonephritis is a relatively common cause of nephrotic syndrome in endemic areas affecting especially male children. When this disease affects girls or women, both the glomerular disease and the hepatitis B carrier state could affect subsequent pregnancies. This may be the first reported case of such a pregnancy. In this patient the partially remitted renal disease and the reduced infectivity of the hepatitis B carrier state decreased the influence of the disease on the pregnancy.

Nephrotic syndrome in Namibian children.

BACKGROUND AND OBJECTIVES: Patterns of nephrotic syndrome vary between regions and countries, and influence approaches to management. In the mid-1970s the University of Stellenbosch became involved in providing tertiary care to Namibia, including a paediatric nephrology service. The aim of this study was to document the clinical, pathological and outcome features of nephrotic syndrome in Namibian children. SUBJECTS: Seventy black Namibian children with nephrotic syndrome were managed from 1975 to 1988. Sixty-eight renal specimens (67 biopsies and 1 autopsy specimen) were evaluated. RESULTS: Twenty-nine of the 70 children (41.4%) were hepatitis B virus (HBV) carriers, of whom 25 (86.2%) were male. Of the 29, 26 had predominantly membranous glomerulonephritis (MGN), 1 mesangiocapillary glomerulonephritis (MCGN), and 1 focal segmental glomerulosclerosis (FSGS); 1 child in advanced renal failure was not biopsied. Five children (7.4%) showed minimal change disease (MCD), 11 (16.2%) FSGS and 15 (22.1%) diffuse mesangial proliferative glomerulonephritis (DMP). The remaining 10 children showed diffuse glomerulosclerosis (6), MCGN (3) and endocapillary proliferative GN (1). Four of the 5 children with MCD went into remission on immunosuppressive treatment. Of the 15 with DMP, 4 improved spontaneously and only 1 of those treated did not improve. Only 2 of those with FSGS improved on treatment. The children with HBV-associated MGN and MCGN were offered symptomatic rather than specific treatment. Thirteen children presented with degrees of chronic renal failure. Eight are known to have died, 3 of relentless nephrotic syndrome and 4 (of whom 3 were HBV carriers) of end-stage renal failure. One child died of penicillin anaphylaxis. CONCLUSIONS: The pattern of nephrotic syndrome in black Namibian children differed greatly from the non-African pattern elsewhere in that MCD was uncommon and HBV-associated GN was the most common single group. The most frequent pattern of HBV-associated GN was MGN with some mesangiocapillary features showing marked male predominance. MCD and DMP were potentially treatable and could only be identified by biopsy. HBV carrier rates exert a major influence on the proportions of morphological subgroups of nephrotic syndrome in children. As these HBV carrier rates alter in future due to the influence of vaccination and urbanisation, the relative size of nephrotic subgroups seems likely to alter.

HIV-associated nephropathy--an initial presentation in an HIV-positive patient.

The lesions of HIV-associated nephropathy occur in patients with AIDS, AIDS-related complex and in individuals clinically asymptomatic for HIV infection. We report on a 35-year-old black South African woman who presented with nephrotic syndrome and renal failure. The renal biopsy appearance suggested HIV infection and this was subsequently verified. This finding emphasises the possibility that otherwise asymptomatic patients presenting with renal disease may be HIV-positive.

Lupus nephritis. Part I. Histopathological classification, activity and chronicity scores.

Renal biopsy has made a major contribution to the understanding and management of patients with lupus nephritis. In a 5-year retrospective study the renal morphology of 55 biopsies from 51 patients with lupus nephritis was classified according to World Health Organisation criteria. In addition, semi-quantitative activity and chronicity scores were documented. The findings were similar to series from other parts of the world. Of the biopsies reviewed, 6 were class II, 13 class III, 32 class IV and 4 class V. In situations of overlap, segmental proliferative features determined the class to which a biopsy specimen was assigned. Twenty-five of the patients, all WHO class IV, showed activity scores in the severe range. Most of the activity score features were common and easily recognised but necrotising angiitis was only seen in 1 patient. Haematoxylin bodies were difficult to document and the nature and value of the haematoxylin body is questioned.

Lupus nephritis. Part II. A clinicopathological correlation and study of outcome.

A 5-year retrospective study of lupus nephritis at Tygerberg Hospital was performed in an attempt to document the clinical and histological spectrum of the disease and to study the outcome of the illness. Activity and chronicity scores were used in addition to the World Health Organisation classification system. Of 55 biopsies from 51 patients reviewed, 6 were class II, 13 class III, 32 class IV and 4 class V. There were 19 deaths and in 15 of these the histological classification was IV. Renal failure and infections, often with uncommon pathogens, were the most important causes of death. Serum creatinine values and creatinine clearance at the time of biopsy or follow-up, and hypertension at follow-up showed a significant relationship with outcome. WHO class IV was associated with a poor outcome (P = 0.048) when compared with the other WHO classes combined. Activity scores showed a significant relationship to the outcome (P = 0.018). The anticardiolipin antibodies IgG and IgM were not associated with WHO class or outcome. The study revealed a spectrum of histological results similar to that of other studies, with a high mortality rate, particularly in class IV disease. Poor renal function, persistent hypertension, histological classification IV, and high activity scores were found to be important prognostic indicators.

A neural network approach to the biopsy diagnosis of early acute renal transplant rejection.

AIMS: To develop and test a neural network to assist in the histological diagnosis of early acute renal allograft rejection. METHODS AND RESULTS: We used three sets of biopsies to train and test the network: 100 'routine' biopsies from Leicester; 21 selected difficult biopsies which had already been evaluated by most of the renal transplant pathologists in the UK, in a study of the Banff classification of allograft pathology and 25 cases which had been classified as 'borderline' according to the Banff classification in a review of transplant biopsies from Oxford. The correct diagnosis for each biopsy was defined by careful retrospective clinical review. Biopsies where this review did not provide a clear diagnosis were excluded. Each biopsy was graded for 12 histological features and the data was entered into a simple single layer perception network, designed using the MATLAB neural network toolbox. Results were compared with logistic regression using the same data, and with 'conventional' histological diagnosis. If the network was trained only with the 100 'routine' cases, its performance with either of the other sets was poor. However, if either of the 'difficult' sets was added to the training group, testing with the other 'difficult' group improved dramatically; 19 of the 21 'Banff' study cases were diagnosed correctly. This was achieved using observations made by a trainee pathologist. The result is better than was achieved by any of the many experienced pathologists who had previously seen these biopsies (maximum 18/21 correct), and is considerably better than that achieved by using logistic regression with the same data. CONCLUSION: A neural network can provide a considerable improvement in the diagnosis of early acute allograft rejection, though further development work will be needed before this becomes a routine diagnostic tool. The selection of cases used to train the network is crucial to the quality of its performance. There is scope to improve the system further by incorporating clinical information. Other related areas where this approach is likely to be of value are discussed.

An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome.

BACKGROUND: The Banff classification for assessment of renal allograft biopsies was introduced as a standardized international classification of renal allograft pathology and acute rejection. Subsequent debate and evaluation studies have attempted to develop and refine the classification. A recent alternative classification, known as the National Institutes of Health Collaborative Clinical Trials in Transplantation (NIH-CCTT) classification, proposed three distinct types of acute rejection. The 1997 Fourth Banff meeting appeared to move towards a consensus for describing transplant biopsies, which incorporated both approaches. Patients who received a renal allograft at the Oxford Transplant Centre were managed by a combination of protocol and clinically indicated biopsies. We have undertaken a retrospective analysis of the biopsies correlated with the clinical outcome to test the prognostic value of the original Banff (Banff 93-95) and NIH-CCTT classifications. METHODS: Three hundred and eighty-two patients received renal allografts between May 1985 and December 1989, and were immunosuppressed using a standard protocol of cyclosporine, azathioprine and steroid. Adequate 5-year follow-up data were available on 351 patients, and of these, 293 had at least one satisfactory biopsy taken between days 2 and 35 after transplantation, the latter patients forming the study group. The D2-35 biopsies taken from these patients, which were not originally reported according to the Banff classification, were re-examined and classified according to the Banff 93-95 protocols. For each patient the biopsy found to be the most severely abnormal was selected, and the Banff and NIH-CCTT grading compared with the clinical outcome. RESULTS: Seven hundred and forty-three biopsies taken from 293 patients between days 2 and 35 after transplantation were examined and the patients categorized on the basis of the 'worst' Banff grading as follows. Normal or non-rejection, 20%; borderline, 34%; acute rejection grade I (AR I), 18%; AR IIA, 6%; AR IIB, 14%; AR III, 1%; AR IIIC, 3%; widespread necrosis 3%. The clinical outcome for the last two groups combined was very poor with 18% of grafts functioning at 3 months and 6% at 5 years. The other groups with vascular rejection (AR IIB and AR III) had an intermediate outcome, graft survival being 78% at 3 months and 61% at 5 years. The remaining four groups (normal, borderline, cellular AR I and AR IIA) had the best outcome: graft survival 95% at 3 months and 78% at 5 years with virtually no difference between the four groups. Three forms of acute rejection, namely tubulo-interstitial, vascular and transmural vascular, were identified, but only the latter two categories were associated with a poor outcome. CONCLUSIONS: The eight sub-categories of the Banff classification of renal allograft biopsies are associated with three different prognoses with respect to graft survival in the medium term. These three prognostic groups correspond to the three NIH-CCTT types. The data provide support for the consensus developed at Banff 97 separating tubulo-interstitial, vascular and transmural vascular rejection (types I, II and III acute rejection).

Infective endocarditis--the effect of liposomes as carrier substance for alpha 1-antitrypsin and ampicillin.

Infective endocarditis has a high mortality and morbidity rate despite all available treatment. Little attention has been paid to the possible role of polymorphonuclear leucocytes in damage to the heart valves. It was postulated that if the elastases set free from these leucocytes could be neutralised, this would prevent damage to the heart valves. Alpha 1-antitrypsin (alpha 1-AT) in liposomes was used to neutralise elastases. This process on its own and in various combinations with ampicillin were compared in animal models. Evaluation was performed by measuring vegetation size, by blood and vegetation cultures, and by light microscopy of the damaged tissue. A statistically significant difference (t-test; P less than 0.005, with Bonferroni's correction for multiple comparisons) was found in vegetation size in the groups receiving ampicillin in liposomes, but the hypothesis that alpha 1-AT might reduce valvular damage was not proven.