The other side of vitamin D therapy: a case series of acute kidney injury due to malpractice-related vitamin D intoxication
.

BACKGROUND: Vitamin D deficiency is highly prevalent in Indian Kashmir. Many people get injectable vitamin D (600,000 IU/injection). At times, the dose prescribed is far above the permissible limit. We report 62 patients with malpractice-related vitamin D intoxication, presenting with hypercalcemia and acute kidney injury (AKI). METHODS: The diagnosis was made on basis of (1) history of multiple intramuscular vitamin D injections (2) toxic serum levels of 25-OH vitamin D and (3) exclusion of common causes of hypercalcemia (malignancy and hyperparathyroidism). Their presentation was either de novo AKI in 51 (group 1) or acute on top of chronic kidney disease in 11 (group 2). RESULTS: The mean age was 60 ± 14 vs. 62 ± 13 years, approximate number of vitamin D injections received ranged from 4 to 28 (2.4 - 16.8 million units) vs. 3 to 24 (1.8 - 14.4 million units), mean creatinine at presentation was 3.2 ± 0.9 vs. 4.5 ± 1.1 mg/dL, which decreased to 1.2 ± 0.2 vs. 3.3 ± 1.0 mg/dL, mean serum calcium on admission was 13.7 ± 1.4 vs. 13.6 ± 2.0 mg/dL which decreased to 10.7 ± 1.2 vs. 11.0 ± 1.0 mg/dL on follow-up of 7.2 ± 0.6 months, mean vitamin D level was 313.3 ± 54.8 (range 235 - 375) vs. 303.7 ± 48.4 (range 210 - 375) nmol/L and mean PTH was 18.1 ± 9.6 (range 6.2 - 32) vs. 52.3 ± 12.6 (range 28 - 88) pg/mL in group 1 vs. group 2, respectively. The clinical presentation was weakness, constipation, abdominal pain, nausea, vomiting, anorexia, altered sensorium, and oliguria. The treatment received was intravenous fluids (normal saline) in all in group 1 and in 8/11 in group 2, short course of steroids (prednisolone) in 44, and bisphosphonate in 6. CONCLUSION: This is the largest case series of AKI secondary to vitamin D toxicity ever reported.
.

Norethisterone-Induced Liver Injury and a Short Survey Among Gynecologists.

Norethisterone, a commonly used oral contraceptive, and treatment for various gynecological disorders such as menorrhagia, abnormal uterine bleeding, and breast cancer, has been associated with multiple liver injuries. These injuries can manifest as hepatitis or cholestatic types of injury, benign neoplasms, peliosis hepatis, sinusoidal obstruction syndrome, and enlargement of existing hemangiomas. This report presents three cases in which liver enzyme levels were elevated due to norethisterone intake. Two of the cases were individuals undergoing evaluation as potential kidney donors in the nephrology department for their spouses, while the third case involved a patient with chronic kidney disease (CKD) stage-5 on maintenance hemodialysis. Regular follow-up of these patients, particularly due to the significance of two being kidney donors and one having advanced CKD, allowed for early detection of asymptomatic liver enzyme elevation and prompt discontinuation of norethisterone. Prescribing norethisterone is common in gynecological settings, including ours. To assess gynecologists' knowledge regarding norethisterone-related side effects, we conducted an online survey, the results of which are discussed in this report.

Primary hyperoxaluria: a case series.

BACKGROUND: Primary hyperoxaluria (PH) is a rare genetic disorder characterized by the excessive production and accumulation of oxalate. We present five cases of PH, each exhibiting varying manifestations of the disorder including a case presenting as postpartum kidney failure. Notably, three of these cases involve a previously unreported mutation. CASE PRESENTATIONS: We evaluated five Indian patients who presented with varying manifestations of PH. The first case, a 30 year old woman, presented as post-partum kidney failure and was found to be having oxalate nephropathy precipitated by dietary oxalate overload in the setting of previously undiagnosed PH. Genetic analysis revealed a previously unreported mutation in the alanine-glyoxylate aminotransferase gene. The patient underwent simultaneous kidney liver transplant. The second and third cases, 26 and 28 year old women respectively, were asymptomatic siblings of the first patient, who were diagnosed through screening. The fourth case is a 12 year boy with PH type 1 presenting as nephrolithiasis and rapidly worsening kidney function requiring combined kidney liver kidney transplant. Case 5 is a 6 year old male child with type 2 PH presenting with nephrolithiasis, nephrocalcinosis and normal kidney function. All the patients were born to consanguineous parents. CONCLUSIONS: Due to limited clinical suspicion and inadequate diagnostic resources in certain countries with limited resources, it is possible for PH to go undiagnosed. The manifestations of the disease can range from no noticeable symptoms to severe disease. Interestingly, in some individuals with primary hyperoxaluria, the disease may not exhibit any symptoms until it is triggered by a high intake of dietary oxalate.

Ambulatory Blood Pressure Monitoring versus Office Blood Pressure Monitoring to Identify the True Hypertension Status of Living Kidney Donors.

Ambulatory blood pressure monitoring (ABPM) is a reliable modality and is preferred over office blood pressure monitoring (OBPM) for detecting hypertension. However, despite its advantages, the utilization of 24-h ABPM in evaluating living kidney donors has not been universally adopted by transplant centers, partly because of the lack of data about the utility of ABPM. This study aimed to identify patients with masked and white-coat hypertension, thereby ensuring appropriate identification of their true hypertension status and assessments of the risk to donors. This study included 73 potential living kidney donors. BP was measured in the office using a standardized protocol as well as by ABPM. Detailed clinical and biochemical parameters were assessed. Target organ damage was assessed in all the donors by assessing proteinuria, hypertensive retinopathy, and echocardiography. Out of the 73 donors, 64.4% were females and 35.6% were males. The average age of individuals in our donor population was 42.0 ± 11.28 years. In total, 31.5% were detected to be hypertensive by OBPM. With ABPM, only 21.9% of donors were hypertensive. The overall prevalence of white-coat hypertension was 30.4%; that of masked hypertension was 6.0%. In donors diagnosed as hypertensive by OBPM, three individuals were identified as having target organ damage. However, two additional donors who were initially missed as hypertensive using OBPM had target organ damage. OBPM overestimated the prevalence of hypertension compared with ABPM. ABPM is the better modality in terms of diagnosing white coats and masked hypertension. ABPM also more reliably correlates with target organ damage than OBPM.

Spectrum of EGFR mutation and its relation with high-risk predictors in thyroid cancer in Kashmiri population: 2 years prospective study at a tertiary care hospital.

BACKGROUND: EGFR mutation has not been extensively studied in thyroid cancer. This study was conducted to study spectrum of EGFR mutation in thyroid cancer in Kashmiri population for possible therapeutic purpose. METHODS: It was 2 years prospective cross-sectional study conducted at a tertiary care center in which histologically confirmed, untreated thyroid cancers were included. These specimens were subjected to EGFR mutation analysis by AS-PCR method. RESULTS: There were a total 60 patients with preponderance of females [44(73%) vs 16(27%)]. Most were in the age group of less than 45 years (75%). Most of these patients were non-smokers [50(83.3%) vs 10 (17.3%)]. Papillary thyroid carcinoma (PTC) was the commonest type 48(80%), rest was follicular type (FTC) 12(20%). Well-differentiated carcinoma (WDC) was common than poorly differentiated (PDC) [41(68.4%) vs 19 (31.6%)]. Lymph node metastasis and vascular invasion were present in 32 (53.4%) and 17 (28.4%) respectively. Thirty-two (53.3%) patients were having 15 bp deletion in exon 19 of EGFR. These deletions were common in PTC than FTC, 29(60.5%) vs 3(25%) which was statistically significant (p = 0.04, CI = 0.2). The total mutational rate of T790M in EGFR tyrosine kinase domain (exon 20) was found to be only 8.4% (5 of 60). Only 4 (8.3%) of these mutations were detected in PTC and rest in FTC (1 of 12). Twenty-six (43.3%) of exon 21 were positive for L858R mutation in EGFR tyrosine kinase domain. Married persons and PDC were significant predictors of L858R mutation in EGFR tyrosine kinase domain in thyroid cancer as this was statistically significant in them with p = 0.04, 0.03 respectively. CONCLUSION: In our population, PTC is common in females with half of population harboring EGFR mutation and it is statistically significant in poorly differentiated carcinoma and in married individuals. It implies that EGFR may be used in thyroid cancer as a possible therapeutic agent in our set of population.

Sero Conversion of Viral Hepatitis among End Stage Renal Disease Patients on Hemodialysis in Kashmir: Results of a Prospective Study.

BACKGROUND: The seroconversion is a significant health concern in patients with end-stage renal disease undergoing hemodialysis particularly in high endemic zones of HBV and HCV. PATIENTS AND METHODS: This prospective study was conducted from January 2009 to April 2018 at Sheri Kashmir Institute of Medical Sciences, Srinagar, Kashmir. A cohort of 459 end-stage renal disease patients on hemodialysis was enrolled from four dialysis centres and followed in a longitudinal manner. Their seroconversion rates, risk factors were studied. Positive patients were treated and followed up. RESULTS: This study demonstrated HBV seroconversion rate of 7.4 % (n = 34) and HCV seroconversion rate of 10% (n = 46) in a cohort of 459 patients on hemodialysis attending four dialysis centres of Kashmir. Patients with diabetes mellitus outnumbered in seroconversion rates of (43.75%) followed by patients with glomerulonephritis (23.75%). Of 15 patients who had undergone renal transplantation 10 (66.67%), patients had seroconversion on hemodialysis which was statistically significant (P < 0.001). Patients who were dialysed at multiple HD centres had significant seroconversion than those who followed up at a single center. Seroconversion was associated with longer duration of dialysis (80.30 ± 30.92 vs 61 ± 9.41months, P < 0.000). HBV vaccination of the ESRD patient on hemodialysis was significantly protective against seroconversion (P = 0.000). CONCLUSIONS: Hepatitis B vaccination, stringent precautions in all dialysis centres could help to reduce the high seroconversion rates which have a high financial burden on ESRD patients. Intense health education to both patients and medical staff will be beneficial to lower the seroconversion rates.

Primary IgA nephropathy in the Kashmiri population.

IgA nephropathy (IgAN) remains one of the most common glomerular lesions, which has a striking geographic distribution and is the most common form of primary glomerular disease in Asia. However, the exact prevalence or clinicopathological spectrum of IgAN in India is not well documented. This retrospective study analyzed the presentation in 126 patients of primary IgAN out of 298 native kidney biopsies (42.28%) performed over a period of three years (2013-2015). The patients were followed up for three months. This is the second highest prevalence recorded in the world after Japan. Among the clinical features of our cohort, the mean age was 31 years, with a male-to-female ratio of 2:1, with the highest incidence observed in the third decade of life in both sexes. The majority of our patients (47%) presented with renal failure with a mean serum creatinine value of 3.1 mg/dL and with burnt out morphology on histo-pathology; 72.2% of patients were hypertensive at presentation. On histopathology, Haas class V (35.5%) had the highest frequency followed by class IV (25.8%). The Oxford MEST score was not applicable in 36 patients because of advanced sclerosis (>50%). In the remaining ninety patients, majority had tubular atrophy and interstitial fibrosis of varying degrees. At three months of follow-up, the patients who had presented with renal failure (47.6%), settled in chronic kidney disease stage III (25.4%) followed by stage IV (18.6%) and stage V (11.8%). Our study in Kashmir suggests that IgAN is more common in the younger age group, with a significant number of patients presenting with advanced renal failure and, on morphology, showing a burnt out disease, with many developing end-stage renal disease. Studies evaluating the underlying factors can have immense importance in dealing with the disease.

von Recklinghausen's neurofibromatosis associated with membranous glomerulonephritis.

A 70-year old woman, known case of von Recklinghausen's neurofibromatosis presented with nephrotic syndrome and mild azotemia. Renal biopsy revealed membranous nephropathy. After ruling out secondary causes of membranous nephropathy, a possible coexistence of von Recklinghausen's neurofibromatosis and membranous nephropathy were thought of. This association has rarely been reported.