Renal outcomes with the newer antidiabetes drugs: the era before and after CREDENCE.

In 2008, the US Food and Drug Administration provided guidance for the evaluation of the cardiovascular safety of antidiabetes drugs. The newer antidiabetes drugs, approved after 2008, were therefore evaluated in long-term cardiovascular outcome trials, designed and powered for the assessment of cardiovascular safety. Accordingly, the primary endpoint of these trials was a cardiac composite endpoint. Since 2008, the data from various cardiovascular outcome trials have been reported, including SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), TECOS (sitagliptin), CARMELINA (linagliptin), CAROLINA (linagliptin), ELIXA (lixisenatide), LEADER (liraglutide), EXSCEL (exenatide once-weekly), SUSTAIN-6 (injectable semaglutide), HARMONY Outcomes (albiglutide), REWIND (dulaglutide), PIONEER-6 (oral semaglutide), EMPA-REG OUTCOME (empagliflozin), the CANVAS Program (canagliflozin) and DECLARE-TIMI 53 (dapagliflozin). Some of these trials subsequently also published data on renal outcomes, although these were secondary or exploratory analyses. Dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists had beneficial effects on albuminuria, while sodium-glucose co-transporter-2 inhibitors additionally showed a positive effect on 'hard' renal outcomes. In contrast to the cardiovascular outcome trials, the renal outcome trial of canagliflozin, CREDENCE, assessed a hard renal endpoint as its primary endpoint and showed positive effects on these hard renal outcomes. In this review, we aim to highlight the renal outcome data from the cardiovascular outcome trials and the CREDENCE trial and understand the differences between their results. The post CREDENCE era would appear to reinforce the position of sodium-glucose co-transporter-2 inhibitors as drugs providing cardiorenal protection, in addition to their anti-glycaemic effects.

Mycophenolate versus Cyclophosphamide for Lupus Nephritis.

Systemic lupus erythematosus is common in our country, and renal involvement is an important cause of chronic kidney disease. This study was aimed at comparing the three regimens, i.e., cyclophosphamide-based regimes (low dose and high dose) and mycophenolate mofetil (MMF)-based regime and determining if cyclophosphamide (CPM)-based regime can be an effective, safe, and cheap alternative to MMF-based regime in a resource-limited setting. Out of 144 patients, females constituted 89%. Nephrotic nephritic presentation was the most common. Rapidly progressive renal failure was seen in in 42 (29.1%) patients. Class IV was the most common 66 (45.8%) histological class. Crescentic glomerulonephritis was seen in 18 (12.5%). Overall remission (complete + partial) at 6 months was seen in 71.4% in National Institute of Health regime, 65% in European lupus nephritis trial protocol and 72.9% in MMF regime. End-stage renal disease and switching to other therapies were comparable among the three groups. Although infections were more with CPM, the difference was not statistically significant. CPM-based therapies were associated with a significantly lower cost.

An unusual case of nephrotic syndrome.

Nephrotic syndrome can be rarely due to inherited disorders of enzymes. One such variety is lecithin cholesterol acyltransferase deficiency. It leads to accumulation of unesterified cholesterol in the eye and other organs. We report a case of nephrotic syndrome with cloudy cornea and hypocholesterolemia with foam cells and lipid deposits on renal biopsy. Awareness about this rare disease may help in the early institution of specific measures to prevent progression to end-stage renal disease.

Splenorenal graft: A safe and effective treatment for renovascular hypertension.

Renovascular hypertension can be managed medically in most cases. However, in cases of failed medical therapy revascularization is indicated. Splenorenal grafting is one such method for revascularization. We present a report of splenorenal grafting for the management of resistant hypertension.

Renal histology in diabetic nephropathy: A novel perspective.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease all over the world. India has a high incidence and prevalence of diabetes and >30% have nephropathy. Recently, a histological classification has been proposed. This study analyzed the renal histology in 114 diabetic patients with renal dysfunction. Nearly 75% of patients had DN. Fifty five (63.95%) were males. Mean duration of diabetes was 7.04 ± 4.9 years. Mean serum creatinine in study group was 5.2 ± 2.9 mg/dl, with mean estimated glomerular filtration rate of 23.43 ± 21.48 ml/min/1.732 m(2). Forty eight patients (55.81%) had diabetic retinopathy (DR); prevalence of DR was more in patients who had diabetes for > 10 years than patients who had diabetes for <6 years (P = 0.022). The most common histological class was Class IV observed in 37 (43.02. %) cases, Class III DN in 24 (27.90%) cases, Class IIa and Class IIb in 11 (12.79%) cases each and Class I DN in 3 (3.48%) cases. Higher histological class was associated with higher proteinuria, lower glomerular filtration rate (P < 0.001) and was more likely to be associated with retinopathy (P = 0.012) and hypertension (P = 0.0003) but did not correlate with duration of diabetes (P = 0.85). There was a poor correlation between retinopathy and DN. Biopsy helps to stage the renal lesions in diabetics with renal dysfunction.

Maternal drugs and neonatal renal failure.

Maternal use of drugs during pregnancy may cause irreversible renal failure in the newborn. This report highlights the adverse effect of telmisartan during the last trimester of pregnancy. The neonate presented with oliguric renal failure and the renal histology showed proximal tubular dysgenesis.

Renal disease in human immunodeficiency virus - Not just HIV-associated nephropathy.

The aim of the study was to determine the various histopathological lesions in human immunodeficiency virus (HIV) patients with renal dysfunction and to establish clinicopathological correlation. Over a period of two years from January 2008 to March 2010, 27 HIV positive patients with renal dysfunction were subjected to renal biopsy. Of the 27 patients, 23 were males and four were females (85.2% males, 14.8% females). Mean age was 38.2 ± 10.36 (range 20 - 60) years. The probable mode of acquisition of HIV infection was sexual in 22 patients (81.5%). Thirteen patients (48%) had nephrotic proteinuria. The CD4 count ranged from 77 to 633/microliter. The kidneys were of normal size in 19 (70.4%) and bulky in eight (29.6%) patients. Thirteen patients required renal replacement therapy. Eleven patients had acute tubule-interstitial lesions (40.7%) while 15 (55.5%) had glomerular lesions. The various glomerular lesions were, focal segmental glomerulosclerosis in five, amyloidosis in three, diffuse proliferative GN in two, and membranoproliferative glomerulonephritis (GN), membranous GN, minimal change disease, diabetic nephropathy, crescentic GN, and thrombotic microangiopathy were seen in one each. None of the clinical or laboratory variables, except hypertension, was found to predict glomerular versus non-glomerular lesions on biopsy. In conclusion we show that a variety of glomerular and tubulointerstitial lesions can be seen on renal histology. Hence, renal biopsy is indicated in renal dysfunction associated with HIV for making proper diagnosis and therapy.

Collagenofibrotic glomerulopathy - Case report with review of literature.

Collagenofibrotic glomerulopathy is a rare, idiopathic glomerular disease characterized by abnormal accumulation of type III collagen fibrils within the mesangial matrix and subendothelial space and a marked increase in serum type III procollagen peptide levels. Proteinuria (commonest feature), edema, hypertension, and occasional progression to end-stage renal disease are the various features of this disease. The etiology and pathogenesis remain elusive. There have been reports of the disease running in the family, suggesting the possibility of genetic transmission. We report two cases of this rare entity.

Refractory rickets in the tropics.

Rickets is an important problem in children. The majority of rickets in children is due to deficiency of calcium, phosphorus or vitamin D. However, rickets may also be a feature of renal diseases, e.g. renal tubular acidosis, hypophosphatemic rickets or rickets associated with renal insufficiency. The treatment varies with etiology and hence complete workup is essential before initiating therapy.

Leprosy in a renal transplant recipient: review of the literature.

A 52-year-old male underwent living-related renal transplantation. He received prednisolone, azathioprine, and cyclosporine as immunosuppression protocol. Eleven years after transplantation, he developed pyrexia with multiple nodular lesions on his limbs, trunk, and face. Skin biopsy and smears showed the presence of numerous acid-fast bacilli with 5% sulfuric acid indicative of Mycobacterium leprae. He was initiated on multidrug therapy (MDT) including dapsone, clofazimine, and rifampicin. After 2 years of MDT, he developed new multiple erythematous, tender subcutaneous nodules in crops over his face and upper limbs. Skin biopsies and histopathological examination confirmed the diagnosis of type 2 lepra reaction or erythema nodosa leprosum. He was managed with an increase in the dose of prednisolone and thalidomide. He was continued on MDT.

P300 as a marker of cognitive dysfunction in chronic epileptics.

P300 event related potential was done in 23 chronic epileptics (12M, 11F) to assess subclinical cognitive impairment. No patient had any obvious neurological abnormality or brain damage. All had normal CT Scans and a mini mental scale score of at least 25. Neuropsychological evaluation done included Bender Gestalt test, Bhatia Battery, Wecshler Memory scale. P 300 event related potential was determined using 'Odd ball paradigm'. P300 latency was significantly increased in chronic epileptics (PCO < 001) compared to controls. There was no relation between P300 latency and amplitude with seizure onset, duration frequency. Nor was there any association between the three neuropsychological parameters and P 300 latency. We conclude subclinical cognitivedysfunction is common in epileptics and P300 event related potential could serve as a marker of cognitive impairment.

Aflatoxin induced testicular degeneration and decreased meiotic index in Rattus norvegicus.

The effect of oral consumption of 200 +/- 100 ppb of crude aflatoxin (B1, B2, G1, G2) showed testicular degeneration and a decrease in the meiotic index.

Time factor as a prognostic indicator on the Bender-Gestalt test.

Z-scores from Bender-Gestalt records of 62 psychiatric in- and outpatients were computed. The patients were put on active treatment, and a psychiatric rating was done to evaluate therapeutic recovery after a period of 19 to 24 months. These patients were grouped into three categories, i.e., patients with low Z-scores and good therapeutic recovery; patients with high Z-scores and poor therapeutic recovery; patients with low Z-scores who still showed poor response to treatment. Total time taken by each patient to reprduce the BG designs was noted as well. Results indicate that Z-score was a significant prognostic indicator for schizophrenics, affective psychotics, organic psychotics and patients who were suffering from anxiety and conversion reactions, but not for obsessive compulsive neurotics. Time taken for BG reproductions proved to be an important prognostic indicator, as patients who did not respond satisfactorily to the treatment took significantly more time than those who responded well to treatment. Hence, time taken by the patients for BG reproductions also needs to be considered when any predictions are made with regard to therapeutic outcome.