Cardiorenal disease management in type 2 diabetes: An expert consensus.

BACKGROUND AND AIM: The interplay between cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes (T2D) is well established. We aim at providing an evidence-based expert opinion regarding the prevention and treatment of both heart failure (HF) and renal complications in people with T2D. METHOD: ology: The consensus recommendations were developed by subject experts in endocrinology, cardiology, and nephrology. The criteria for consensus were set to statements with ≥80% of agreement among clinicians specialized in endocrinology, cardiology, and nephrology. Key expert opinions were formulated based on scientific evidence and clinical judgment. RESULTS: Assessing the risk factors of CVD or CKD in people with diabetes and taking measures to prevent HF or kidney disease are essential. Known CVD or CKD among people with diabetes confers a very high risk for recurrent CVD. Metformin plus lifestyle modification should be the first-line therapy (unless contraindicated) for the management of T2D. Glucagon-like peptide 1 (GLP-1) agonists can be preferred in people with atherosclerotic cardiovascular disease (ASCVD) or with high-risk indicators, along with sodium-glucose cotransporter-2 inhibitors (SGLT2i), whereas SGLT2i are the first choice in HF and CKD. The GLP-1 agonists can be used in people with CKD if SGLT2i are not tolerated. CONCLUSION: Current evidence suggests SGLT2i as preferred agents among people with T2D and HF, and for those with T2D and ASCVD. SGLT2i and GLP-1RA also lower CV outcomes in those with diabetes and ASCVD, and the treatment choice should depend on the patient profile.

Plasmapheresis for Pulmonary Hemorrhage Following Viperine Snakebite: A Case Report with Review of Literature.

INTRODUCTION: Snakebites are one of the commonest occupational hazards in tropical countries and viperine bites are potential to cause systemic toxicity. Coagulopathies and acute kidney injury (AKI) have been documented and easily dealt with in past, but pulmonary hemorrhage has been rarely seen and plasmapheresis has shown promising result for the same. This case reports highlight the effective use of plasmapheresis for pulmonary hemorrhage post-snakebite. BACKGROUND: Viperine snakebite has been associated with high morbidity and mortality due to its toxic systemic envenomization. The important systemic manifestations are coagulopathy, neuromuscular paralysis, AKI, myotoxicity, and cardiovascular collapse. Antivenomization, renal replacement therapy, steroids, and other supportive care are considered to be the mainstay of treatment till date. Pulmonary hemorrhage has been an unusual manifestation of viper bite and rarely reported and steroids have been used in such scenario but with mixed results. Role of plasmapheresis has been documented in the management of snakebite but especially for hematological problems and in limb preservation/salvage strategies. The use of same, for pulmonary hemorrhage has not been studied yet. Here, we present a rare case of pulmonary hemorrhage along with renal failure following viper bite which was successfully treated with plasmapheresis. To the best of our knowledge, it is a rare presentation and has not been reported in the literature reviewed till date. CASE DESCRIPTION: A previously healthy, 36-year-old man presented to our hospital 48 hours after a viper bite. He developed local as well systemic manifestations evident as hemolysis and renal failure. Gradually, he started having hemoptysis followed by respiratory failure requiring ventilatory support. CT chest done was s/o bilateral pulmonary hemorrhages correlating clinically with ongoing tracheal bleed. He had no other bleeding manifestations and had normal coagulation profile. He was initially treated with methylprednisolone therapy, but then did not show any improvement and finally plasmapheresis was done as rescue therapy. Following this, he had improvement in respiratory parameters and settling tracheal bleed with resolution of radiological changes. He was successfully weaned off from the ventilation and also his renal failure also improved with near normalization of pulmonary and renal functions. CONCLUSION: This case highlights the unusual presentation of pulmonary hemorrhage in a patient with viperine bite with normal coagulation and was aggressively managed with plasmapheresis. Hence, plasmapheresis can be used as life-saving modality in patients with systemic envenomization post-viperine bit. HOW TO CITE THIS ARTICLE: Sampley S, Sakhuja V, Bhasin D, Singh K, Singh H. Plasmapheresis for Pulmonary Hemorrhage Following Viperine Snakebite: A Case Report with Review of Literature. Indian J Crit Care Med 2020;24(10):986-990.

Cytomegalovirus Infection in Postrenal Transplant Recipients: 18 Years' Experience From a Tertiary Referral Center.

BACKGROUND: Cytomegalovirus (CMV) reactivation or infection is one of the most important infectious complications in transplant recipient leading to significant morbidity and mortality. Its early detection and prompt treatment is imperative to improve transplant outcome. The present study estimated the frequency of CMV in renal transplant recipients (RTR). Various aspects of pp65Ag assay and quantitative real-time polymerase chain reaction (qRT-PCR) were evaluated in relation to the recent guidelines for CMV detection and treatment. METHODS: Retrospectively, data of clinically suspected cases of CMV (1610 out of total 2681 renal transplants) were analyzed along with a comparison of pp65Ag assay and qRT-PCR. RESULTS: The overall incidence of CMV syndrome was 14.25%; however, the incidence of CMV viremia in the clinically suspected group was 23.73%. The proportion of positive cases with pp65Ag assay and qRT-PCR were 13.6% (95% CI; 7.9-22.3) and 19.3% (95% CI; 12.4-28.8) with a substantial agreement (Cohen's kappa = 0.632) between the 2 techniques. CMV positive recipients were treated with ganciclovir until their viral count was negative or up to 3 weeks, followed by 3 months of prophylaxis with valganciclovir. No graft failure or mortality was reported secondary to CMV infection until 3 to 5 years of follow-up. RESULTS: CMV infection is quite prevalent in RTR, and early detection and immediate treatment or prophylaxis is of utmost importance. qRT-PCR is the gold standard and preferred over other methods; however pp65Ag assay still holds its importance in low-economic countries and populations where CMV infection is more prevalent and financial constraints are a major limitation.

Pretransplant HbA1c and Glucose Metabolism Parameters in Predicting Posttransplant Diabetes Mellitus and Their Course in the First 6 Months After Living-Donor Renal Transplant.

OBJECTIVES: Posttransplant diabetes mellitus is a common and serious metabolic complication after renal transplant. Patients with uremia are known to have abnormal glucose metabolism characterized by insulin resistance and defects in insulin secretion, which are ameliorated to some extent with renal replacement therapy and more so with renal transplant. However, the diabetogenicity of calcineurin inhibitors compounds this state of dysglycemia and promotes the development of diabetes in some patients. It is not clear whether pretransplant dysglycemia is a risk factor for posttransplant diabetes mellitus and, if so, which between insulin resistance and pancreatic ß-cell dysfunction is a major determinant in predicting posttransplant diabetes mellitus. Here, we examined the roles of the pretransplant oral glucose tolerance test, glycated hemoglobin (HbA1c) levels, and homeostatic model assessment-derived insulin resistance and beta-cell function in the prediction of posttransplant diabetes mellitus and the course of these indexes posttransplant. Our aim was to examine the correlations between these factors and their changes posttransplant with the development of posttransplant diabetes mellitus. MATERIALS AND METHODS: Pretransplant fasting blood was drawn from patients for plasma glucose, insulin, C-peptide, and HbA1c levels, which was followed by a 2-hour oral glucose tolerance test. After transplant, patients were followed for 6 months to detect posttransplant diabetes mellitus. Serum insulin, C-peptide, and glycated hemoglobin levels were reexamined in patients with posttransplant diabetes mellitus at 1 and 6 months. RESULTS: Twenty-one patients (29%) developed posttransplant diabetes mellitus. Pretransplant HbA1c was associated with development of posttransplant diabetes mellitus (odds ratio 27.04) on logistic regression. Homeostatic model assessment-derived insulin resistance improved significantly at 6 months posttransplant, whereas beta-cell function remained lower than pretransplant levels in patients with posttransplant diabetes mellitus. CONCLUSIONS: Pretransplant HbA1c may be used as a predictive marker for posttransplant diabetes mellitus. Insulin resistance but not beta-cell function improves in patients with posttransplant diabetes mellitus at 6 months posttransplant.

Two-Year Follow-up Study of Membranous Nephropathy Treated With Tacrolimus and Corticosteroids Versus Cyclical Corticosteroids and Cyclophosphamide.

INTRODUCTION: Both cCTX/GCs and CNIs are recommended as first-line agents in the management of PMN. The present study is an extended report of patients randomized to receive TAC/GCs or cCTX/GCs at 2 years post randomization. METHODS: Seventy patients enrolled in the clinical trial Tacrolimus Combined With Corticosteroids Versus Modified Ponticelli Regimen in Treatment of Idiopathic Membranous Nephropathy: Randomized Control Trial were followed quarterly between 12 and 24 months. At the end of 24 months, 3 patients were lost to follow-up. RESULTS: At 18 months, 66% and 89% (P = 0.04) were in remission in TAC/GCs and cCTX/GCs groups, respectively. At 18 and 24 months, 60% and 86% (P = 0.03) of cases were in remission in the TAC/GCs and cCTX/GCs groups, respectively. At 18 months, 57% and 83% (P = 0.03) of the patients in TAC/GCs and cCTX/GCs groups were in remission without need of any additional immunosuppression (persistent remission) and, at 24 months, 43% and 80% (P = 0.002) were in persistent remission in TAC/GCs and cCTX/GCs groups, respectively. Relapse rate after any remission was 40% and 6.7% in TAC/GCs and cCTX/GCs groups, respectively (P = 0.007). There was an association of aPLA2R titers with remission or resistance (P = 0.006) in relapsing PMN. The significant decrease in eGFR after 12 months of TAC/GCs therapy normalized at 18 and 24 months. DISCUSSION: At 2 years after randomization, relapse rates are higher for TAC/GCs compared with cCTX/GCs in PMN patients. Thus, cCTX/GCs are better than TAC/GCs in the longer term in PMN patients.

Non-imaging assisted insertion of un-cuffed, non-tunneled internal jugular venous catheters for hemodialysis: Safety and utility in modern day world.

BACKGROUND: Absolute necessity in acute kidney injury (AKI) and ignorance in chronic kidney disease (CKD) make the use of un-cuffed, non-tunneled catheters an indispensable vascular access for hemodialysis. Although these catheters should be inserted under radiological guidance, it may not be feasible in certain circumstances. The aim of the present study was to evaluate safety and outcome of non-imaging assisted insertion of these catheters in internal jugular vein (IJV) for hemodialysis. METHODS: We analyzed 233 attempts of non-imaging assisted un-cuffed, non-tunneled IJV catheterization at our center. The immediate insertion complications, duration of use, rate and type of infection and other complications were assessed. RESULTS: Out of the 233 attempts, 223 (213-right, 10-left) were successful. The most common indication was AKI (n = 127, 54.5%), followed by CKD (n = 99, 42.5%). Successful catheterization at first attempt was achieved in 78.9%. Insertion complications were noted in 12.8% and included arterial puncture (5.2%), hematoma (3.0%) and malposition (2.1%). Amongst 219 catheters followed for 4825 days, the mean duration of use was 22 days. Catheter related infections occurred in 42 patients with an incidence of 8.7 per 1000 catheter days. Bacteraemia was present in 10/36 cases (27.7%), positive catheter tip cultures in 71.4% cases and staphylococcal species were the most common organism. Cumulative hazard analysis by Cox regression revealed a linear increase in the risk for infection with each week. CONCLUSION: Non-imaging assisted insertion of uncuffed, non-tunneled catheters is associated with slightly higher rate of insertion complication but comparable outcome in terms of infection rate or days of use.

A prospective study of collapsing focal segmental glomerulosclerosis.

Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to end-stage renal disease (ESRD). We evaluated the clinicopathological spectrum of cFSGS and compared its clinical behavior to steroid and tacrolimus (TAC)-resistant noncollapsing focal segmental glomerulosclerosis (FSGS). All patients (>14 years) diagnosed with cFSGS were enrolled in the study. Staining for differentiated podocyte markers such as WT 1, PAX and KI67 were performed in all patients. The outcome and histological features of cFSGS was compared with a prospectively followed cohort of steroid and TAC-resistant noncollapsing FSGS. The study included 22 cFSGS patients and 19 cases of steroid and TAC-resistant FSGS. Complete remission, partial remission, steroid resistance, progression to ESRD and death were observed in 13.6%, 4.5%, 27.3%, 36.4% and 18.2% patients, respectively. Patients with cFSGS had higher serum creatinine and more advanced tubulointerstitial changes compared to resistant FSGS. Twenty-six percent of therapy resistant noncollapsing FSGS progressed to ESRD after two years of stopping TAC. However, there was no difference in progression to ESRD between cFSGS and therapy-resistant noncollapsing FSGS at the end of two years. Glomerular collapse in the setting of FSGS is poorly responsive to treatment and has a high rate of progression to ESRD. The long-term prognosis of cFSGS and steroid and TAC-resistant FSGS are similar.

Correlates of hematuria on glomerular histology and electron microscopy in IgA nephropathy.

BACKGROUND: Hematuria is the most important clinical manifestation of IgA nephropathy. This study was undertaken with the objective to describe the spectrum of histological changes with reference to the Oxford classification and the ultrastructural changes in the glomerular basement membrane and to correlate them with hematuria. METHODS: 66 patients who underwent renal biopsy for IgA nephropathy were evaluated histologically by the Oxford system and also subject to electron microscopic examination for glomerular immune deposits, as well as alterations in the glomerular basement membrane. RESULTS: On comparing the histological scores generated by the Oxford classification with degree of hematuria, it was found that the status of 'endocapillary proliferation' and the status of 'tubular atrophy and interstitial fibrosis showed a significant correlation. Correlation of hematuria with location of the deposits, i.e. mesangial only, and mesangial with capillary wall deposits (subendothelial and subepithelial) did not show any association. Other alterations of the GBM were seen in 12 cases. The changes included thinning alone in 4 cases, thinning and lamellar splitting in 5 cases, and lamellar splitting alone in 2 cases. CONCLUSION: At presentation, endocapillary proliferation is one histological parameter which shows close association with hematuria.

Early recurrence of proliferative glomerulonephritis with monoclonal immunoglobulin deposits in a renal allograft.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs) is a clinico-pathologic entity, the recurrence of which in the renal allograft has only recently been described. A 55-year-old male presented with rapid deterioration of renal function. Light microscopy showed membranoproliferative glomerulonephritis with kappa light chain restriction and only one sub-class of IgG. He subsequently underwent renal transplant. Two months later, he developed acute graft dysfunction. Renal biopsy showed a recurrence of the disease. Work up for multiple myeloma was positive. Membranoproliferative pattern of injury in the posttransplant setting has a wide range of differential diagnosis, PGNMID being one of them.

Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis.

No previous study has compared mycophenolate mofetil (MMF) with low-dose cyclophosphamide (CYC) in the treatment of lupus nephritis (LN). To do so, we recruited patients with LN (class III, IV, or V) and randomized them to receive either low-dose CYC or oral MMF. Those with crescentic LN, a serum creatinine over 265 µmol/l, and neurological or pulmonary lupus were excluded. MMF was prescribed at daily doses of 1.5-3 g for 24 weeks, while CYC was administered as six fortnightly infusions of 500 mg each. All patients received three methylprednisolone injections, followed by oral corticosteroids. Maintenance therapy with azathioprine and low-dose corticosteroid was started at end of induction therapy. The primary end point was treatment response at 24 weeks, while secondary end points were complete remission, Systemic Lupus Erythematosus Disease Activity Index and adverse events. Of the 173 patients recruited, 100 were equally randomized to receive either CYC or MMF. Baseline characteristics were similar, except for higher 24 h proteinuria in the CYC group. At 24 weeks, 37 patients in each group achieved the primary end point. The complete remission rate was 50% in CYC and 54% in MMF group. Gastrointestinal symptoms were significantly more frequent in patients receiving MMF (52 vs. 4%). However, other adverse events were similar. Thus, low-dose intravenous CYC is comparable in safety and efficacy to oral MMF in the induction treatment of less severe LN.

Pauci-immune glomerulonephritis: does negativity of anti-neutrophilic cytoplasmic antibodies matters?

AIM: A significant proportion of pauci-immune glomerulonephritis (PIGN) patients are reported to have absence of anti-neutrophilic cytoplasmic antibodies (ANCA). However, studies are controversial regarding their significance and there is limited data after the new prognostic classification of PIGN. METHODS: Renal biopsy-proven cases of PIGN were included and their clinical details, ANCA status by immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), Birmingham Vasculitis Activity Score (BVAS) and treatment outcomes at 6 months were noted. The renal biopsies were classified according to the proposed histopathological classification. Scoring was done from 0-3 for interstitial edema, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and arteriosclerosis. The percentage of glomeruli with sclerosis, cellular and fibrous crescents, and percentage of subjects with glomerulitis, tuft necrosis, interstitial granuloma and vasculitis were noted. RESULTS: Out of the 84 subjects included in the study, 33 (39.3%) were negative for ANCA by both IIF and ELISA. These subjects had significantly higher renal involvement, less extra-renal manifestations and lower BVAS. On histology, they had significantly higher proportion of crescentic class (66.7% vs. 41.2%, P = 0.039), higher number of cellular crescents (66.12% vs. 53.3%, P = 0.00008), higher IFTA (1.53 vs. 1.02, P = 0.009) and less interstitial edema (1.44 vs. 1.96, P = 0.003). The treatment outcomes were worse in ANCA-negative PIGN subjects, with significantly less improvement (37.2% vs. 62.8%, P = 0.02), more deterioration (40.7% vs. 14%, P = 0.006), and reduced probability of becoming dialysis free (31.6% vs. 69.6% P = 0.009). CONCLUSIONS: A negative ANCA in PIGN is associated with crescentic class, more IFTA and poor treatment outcomes.

PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians.

BACKGROUND: Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. METHODS: A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by TaqMan assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. RESULTS: Of 114 patients, 66.7% showed elevated serum anti-PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti-PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. CONCLUSION: To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy.

Tacrolimus combined with corticosteroids versus Modified Ponticelli regimen in treatment of idiopathic membranous nephropathy: Randomized control trial.

AIM: There have been very few studies comparing cyclophosphamide (CTX) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy (NIST) resistant idiopathic membranous nephropathy (IMN). The present study was aimed at comparing the efficacy and safety of tacrolimus (TAC)/steroids with cyclical CTX/steroids (Modified Ponticelli regimen (MPR)) in patients with IMN. METHODS: Idiopathic membranous nephropathy patients (n = 70) with persistent nephrotic syndrome after at least 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally randomized to receive TAC with oral prednisolone (TAC*) or MPR. Antibodies against m-type phospholipase A2 receptor (PLA2R Ab) were tested for at baseline and, at 6 and 12 months after the start of therapy. The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups. RESULTS: Intention-to-treat analysis showed that remissions at the end of 6 (74% with TAC* vs. 60% with MPR; P = 0.30) and 12 months (71% with TAC* vs. 77% with MPR; P = 0.78) were comparable. PLA2R Ab titres at 6/12 months correlated with urine protein (r 0.54/0.58) and serum albumin (r -0.49/-0.53) at the end of therapy. Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity. CONCLUSION: In NIST refractory IMN, both TAC* and MPR are comparable, but with different adverse effect profile. PLA2 R Ab has a very good association with proteinuria, and should be regularly monitored on clinical follow-up.

Sequential changes in bone biochemical parameters and bone mineral density after renal transplant.

To evaluate sequential changes in biochemical bone parameters, parathyroid hormone (iPTH), vitamin D levels and bone mineral density (BMD) over a period of 24 weeks after renal transplantation, we studied 75 patients (58 males, with a mean age of 35.4 years) who underwent their first renal transplantation without a past history of parathyroid surgery or fractures. Serum calcium, phosphorus and albumin were measured before transplant, then weekly for four weeks and monthly for the following 20 weeks. Serum iPTH and vitamin D levels and BMD were measured at baseline and 24 weeks after transplantation. After transplantation, there was a significant fall in serum calcium in the first week, followed by a gradual rise. At 12 and 24 weeks, respectively, 17.5% and 8% patients had hypercalcemia. Serum phosphorus decreased after transplant and at 24 weeks; 25% patients had hypophosphatemia. The iPTH levels declined significantly from 251 ± 218.2 pg/mL before transplant to 97 ± 142.8 pg/mL at the end of the study period. At 12 and 24 weeks, 42.7% and 51.3% patients, respectively, had persistent hyperparathyroidism (HPT). Elevated baseline iPTH levels and graft dysfunction were the risk factors for HPT at 12 weeks, while low vitamin D levels were the risk factor at 24 weeks. The BMD showed a significant decline of 2.7% after transplant, and it negatively correlated with the pre-transplant iPTH levels; the patients who received tacrolimus immunosuppression had a lower decline in BMD than the rest of the patients. No fractures were reported during the study period. We conclude that, after renal transplantation, hypercalcemia and hypophosphatemia are common, while a significant proportion of patients have persistent HPT and decline in bone mineral density.

Clinico-pathologic spectrum of C3 glomerulopathy-an Indian experience.

BACKGROUND: C3 glomerulopathy (C3GP) is characterized by deposition of complement C3 with absence/traces of immunoglobulins in the glomeruli and categorized into dense deposit disease (DDD), C3 glomerulonephritis (C3GN), complement factor H related protein 5(CFHR5) nephropathy etc. Collaborative efforts of pathologists, complement biologists and nephrologists worldwide are expanding the histomorphological pattern and laboratory findings related to C3GP. Hence, we studied point prevalence and morphological spectrum of C3GP in Indian patients to correlate morphological patterns with standard therapies and outcome of the patients. METHODS: Retrospective analysis of renal biopsies (2007-2012,n-4565), which on immunofluorescence (IF) had C3 dominant deposits with absence or trace amount of immunoglobulin was carried out. Histopathology and electronmicroscopy (EM) were reviewed; cases were re-classified as DDD and C3GN. Histomorphological patterns of both groups were compared and correlated with treatment. Clinical details and follow up of patients were retrieved from the department of nephrology. RESULTS: There were 31 cases (0.7%) of C3GP sub-classified as DDD (n-13) and C3GN (n-14). It was difficult to sub-classify 4 cases since EM showed overlapping features. C3GN and DDD had distinct clinical characteristics and disease outcome, though pathological features were overlapping. Majority of C3GP patients were males and were in 2(nd) to 4(th) decade of life. Nephrotic syndrome in DDD and nephritic-nephrotic presentation in C3GN patients was more common. Hypertension and oliguria were more often observed in C3GN than DDD. Membranoproliferative pattern (MPGN) was commonest pattern in DDD; other patterns seen were mesangial proliferative, mesangial expansive/nodular, exudative and crescentic. C3GN also had all the above patterns, the predominant ones being MPGN and mesangial proliferative. Limited follow-up revealed response to therapy only in C3GN (33%). Progression to ESRD was 33% in DDD and 10% cases in C3GN. CONCLUSION: C3GP comprise 0.7% of all renal biopsies. MPGN pattern was the commonest morphological pattern in DDD whereas MPGN and mesangial proliferative pattern were equally dominant patterns in C3GN. EM of 4 cases (13%) showed intermediate features. Evaluation of alternate complement pathway must be done in all cases to identify the point of dysregulated alternate complement pathway and to confirm the diagnosis in ambiguous cases. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1730070964135632.

Histopathological indicators of disease outcome in class IV lupus nephritis: a revisit of various indices.

Current management guidelines for lupus nephritis (LN) do not attach importance to histological indices of disease activity or chronicity. The present study was performed to evaluate the clinical relevance of these indices in determining outcomes in patients with class IV LN. We analyzed the data of all patients with biopsy-proven class IV LN seen over a 6-year period. The histopathological findings were reviewed; the activity and chronicity indices proposed by Austin [AI (Austin) & CI (Austin)] and the renal biopsy index proposed by Hill were calculated. As immunofluorescence was not done in all patients, this was excluded from calculation of the renal biopsy index, which was referred to as the modified Hill's index (MHI), which was a composite of glomerular activity index (GAI), chronicity index (CI) and tubulo-interstitial activity index (TIAI). Pearson's correlation coefficient, multilinear regression analysis and logistic analysis were performed, and p value of <.05 was considered significant. During the study period, 114 cases of LN were evaluated, of which 64 % (73/114) had class IV LN. The mean age was 26.5 years, and 92 % were females. The mean scores of AI (Austin), CI (Austin), GAI, CI, TIAI and MHI were 8.46, 2.50, 7.54, 3.06, 4.74 and 2.23, respectively. Serum creatinine correlated significantly with TIAI, CI, CI (Austin) as well as MHI, but not with AI (Austin) or GAI. The serum creatinine level was the strongest clinical parameter determining outcome, while none of the histological indices correlated with either treatment outcome or mortality. None of the histological indices performed better than serum creatinine level in determining the treatment outcomes and mortality.

Correlation of proteinuria with podocyte foot process effacement in IgA nephropathy: an ultrastructural study.

BACKGROUND: Proteinuria is an uncommon clinical manifestation of IgA nephropathy and is usually seen in cases with severe lesions like endocapillary proliferation. However, it is occasionally seen even with cases with mild glomerular manifestations and may even be of nephrotic range. PREDICTOR: Podocyte foot process effacement. OUTCOME: Severity of proteinuria. MEASUREMENTS: Podocyte foot process effacement was measured. Morphometric analysis was performed on transmission electron microscope images using a computerized digital photomicrograph system (BioWizard 4.2 Image analysis software, New Delhi, India). Proteinuria was measured quantitatively assigned into five grades. RESULTS: It was found that as the extent of proteinuria increased, the effacement ratio also increased, and this was most significant between "no" proteinuria and the rest of the categories. CONCLUSION: Nephrotic presentation in IgA nephropathy is a known phenomenon and in certain cases may show near normal glomerular morphology with severe foot process effacement on EM being the only significant finding to explain the proteinuria. Proteinuria in these cases shows a significant correlation with degree of foot process effacement. Renal biopsy is important in these cases because they are known to have a better prognosis and are usually steroid responsive.