Manish Rathi

Natural Medicines Causing Acute Kidney Injury

The use of alternative remedies derived from plants and animals is increasing worldwide. Their source and composition varies depending on the prevalent local practices. They are not tested for efficacy and safety; their ingredients are unknown and the dosage and route of administration are not standardized. Potentially toxic chemicals are added to them to increase their potency and mistaken identity has led to the use of toxic plants instead of the originally intended herb. Kidneys play a vital role in the metabolism and excretion of these substances and acute kidney injury is a common and important manifestation of their toxicity. The most usual renal lesions include acute tubular necrosis, cortical necrosis, and interstitial nephritis. Patients often present late to hospitals with multi-organ involvement. The diagnosis may be missed if the history is not sought specifically. These factors culminate in high mortality rates. Study of this entity is difficult because of the remoteness of the areas, unfamiliarity with local cultures, and mystery and secrecy surrounding the natural medicines used. Physicians need to be aware of this condition to make a timely diagnosis and provide appropriate management. Public awareness and regulation of the use of these medicines are required to eradicate this entity from the community.

Sexual and gonadal dysfunction in chronic kidney disease: Pathophysiology

Sexual and gonadal dysfunction/infertility are quite common in patients with chronic kidney disease. Forty percent of male and 55% of female dialysis patients do not achieve orgasm. The pathophysiology of gonadal dysfunction is multifactorial. It is usually a combination of psychological, physiological, and other comorbid factors. Erectile dysfunction in males is mainly due to arterial factors, venous leakage, psychological factors, neurogenic factors, endocrine factors, and drugs. Sexual dysfunction in females is mainly due to hormonal factors and manifests mainly as menstrual irregularities, amenorrhea, lack of vaginal lubrication, and failure to conceive. Treatment of gonadal dysfunction in chronic kidney disease is multipronged and an exact understanding of underlying pathology is essential in proper management of these patients.

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.

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 therapy in adult-onset steroid-resistant nephrotic syndrome due to a focal segmental glomerulosclerosis single-center experience

INTRODUCTION Management of adults with steroid-resistant (SR) nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is a challenging task. Is tacrolimus (TAC) effective in this situation without serious adverse effects? This prospective study was done to answer this question. MATERIALS AND METHODS In patients with SR nephrotic syndrome due to FSGS, oral TAC (0.1 mg/kg/day) was started targeting a trough level of 5-10 ng/mL along with oral prednisolone (0.15 mg/kg/day) for 48 weeks. In patients with complete remission (CR), TAC dose was reduced to a target of 3-6 ng/mL whereas in partial responders, TAC trough levels were kept at 5-10 ng/mL. TAC was discontinued in those with no remission at 24 weeks and was deemed TAC resistant. Outcome, namely CR and partial remission (PR), was assessed at the end of 24 and 48 weeks. All patients were prospectively followed for 60 weeks. Relapses after CR or PR were recorded; adverse effects, namely nephrotoxicity (>25% rise in creatinine), cosmetic effects, infections and hyperglycemia, were recorded every month. RESULTS A total of 44 SR-FSGS [not otherwise specified 33 (75%), tip lesion 03 (6.8%) and cellular variant 8 (18.1%)] were analyzed. Mean age was 25.16 ± 8.26 (18-51) years. Of 44 patients, CR and PR were achieved in 17 (38.6%) and 06 (13.6%) patients, respectively. TAC resistance was seen in 21 (47.7%) patients. Time taken to achieve remission was 15.2 ± 6 weeks. Five (21.7%) patients with CR had relapse on tapering the dose and seven (30.4%) after stopping TAC. Reversible nephrotoxicity was seen in seven (15.9%) and irreversible in four patients (9%). TAC-related diarrhea was the problem in 10 (22.7%), and infections were seen in 19 patients (43.1%). Impaired fasting glucose and diabetes mellitus were seen in 10 patients (22.7%). CONCLUSION TAC is an effective agent in the management of SR-FSGS. However, strict renal function and blood sugar monitoring is required due to its potential nephrotoxicity and diabetogenic potential.

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

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.

Association between -1486 T>C and +1174 G>A single nucleotide polymorphisms in TLR9 gene and severity of lupus nephritis.

Signaling through Toll-like receptor-9 (TLR9), a mediator of innate immune responses, could have a role in the pathogenesis of systemic lupus erythematosus (SLE). Some studies have shown an association between polymorphisms in the TLR9 gene and disease manifestations. We investigated whether two single nucleotide polymorphisms (-1486 T>C and +1174 G>A) in the TLR9 gene are associated with the risk of renal involvement in SLE. DNA samples from 112 SLE patients (62 with lupus nephritis) and 100 healthy controls were obtained. TLR9 polymorphisms (-1486 T>C and +1174 G>A) were analyzed by polymerase chain reaction–restriction fragment length polymorphism. Genotype and allelic frequencies were compared between lupus patients and healthy controls. Clinical and laboratory manifestations and activity scores on renal biopsy of patients with lupus nephritis were compared between various genotypes. There was no difference in the frequency of genotype or allele distribution at either of the two loci between lupus patients and controls and in lupus patients with or without nephritis. Patients with CC/CT genotype at the -1486 position had higher serum creatinine (P = 0.03) and Austin activity scores (P = 0.015). Patients with AA/AG genotype at +1174 position showed higher serum creatinine (P = 0.04), proteinuria (P = 0.011), anti-dsDNA titers (P < 0.001) and Austin activity scores (P = 0.003) than the GG genotype. Variations at the -1486 and +1174 positions of TLR9 gene are not associated with increased risk of SLE or that of kidney involvement in North Indians. CC/CT genotypes at -1486 and AA/AG at +1174 positions are associated with more severe kidney disease at presentation.

Bardet-Biedl syndrome with end-stage kidney disease: A case report and review of literature

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive condition characterized by retinitis pigmentosa, postaxial polydactyly, central obesity, and renal involvement. Renal failure is the commonest cause of death. We report the first case of BBS with documented end-stage kidney disease from India. The diagnosis had been missed until the patient presented at our hospital. The relevant literature has also been reviewed.

Acute kidney injury due to acute cortical necrosis following a single wasp sting.

Acute kidney injury (AKI) can develop after multiple wasp or bee stings. The etiology is the acute tubular necrosis secondary to shock, pigment toxicity, interstitial nephritis, or direct nephrotoxicity of venom. We report a 40-year-old female who presented with oliguric AKI after a single wasp sting on her hand. Her history, examination, and investigations did not support any of the established causes of AKI in such settings. She did not improve with supportive management and dialysis, and kidney biopsy showed acute cortical necrosis (ACN). This is the first report of ACN after a single wasp sting.

Rheumatological diseases and kidneys: a nephrologist's perspective

Renal involvement is a common occurrence in subjects with rheumatological diseases and can develop either due to the disease itself or secondary to drugs used in the treatment. The prevalence of renal involvement and its severity depends on the underlying disease as well as aggressiveness of the therapy. For most rheumatological diseases, renal involvement heralds a poor prognosis and warrants aggressive immunosuppressive treatment. Thus, it is important to diagnose and manage them at an early stage. On the other hand, patients with primary kidney disease can also develop rheumatological manifestations which need to be differentiated from the former. This article provides the nephrologists perspective upon various rheumatological disorders and associated renal involvement with the aim of sensitizing the rheumatological community about them, resulting in better management of these subjects.