Shivendra Singh

Causes of death in renal transplant recipients with functioning allograft

The survival of transplant recipients is significantly lower than age-matched controls in the general population. The aim of this study was to analyze the trends in mortality of renal allograft recipients at our centre. We retrospectively analyzed data from all patients who were transplanted between October 1988 and June 2010 and were followed at our center. Patients were considered to have death with graft function (DWGF) if death was not preceded by return to dialysis or re-transplantation. The study included 98 renal allograft recipients (male : female – 7.99 : 1). The mean recipient and donor ages were 35.06 ± 11.84 (range: 15–69) and 41.17 ± 10.44 (range: 22–60) years, respectively. Basic kidney diseases were CGN (chronic glomerulonephritis) (60.20%), CIN (chronic interstitial nephritis) (15.31%), DN (diabetic nephropathy) (8.16%), ADPKD (autosomal dominant polycystic kidney disease) (2.04%) and others (14.29%). They were followed up for a mean 79.91 ± 60.05 patient-months. Mortality occurred in 25 (25.51%) patients (male : female – 4 : 1). Causes of death were sepsis/infection (36%), coronary artery disease (28%), CVA (8%), failed graft (4%), and rest unknown (24%). DWGF was 88% of total death and contributed to 78.57% of total graft loss. Overall patient survival at 1, 5, 10, and 15 years were 90.8%, 80.2%, 65.6%, and 59.1%, respectively (Kaplan–Meier analysis). Those who died exhibited significant differences in recipients age (median 40 years vs 31 years, P=0.007), pretransplantation hypertension (HTN) (100% vs 65.75%, P<0.001), post-transplant infection (76% vs 42.47%, P=0.005), coronary artery disease (28% vs 1.37%, P<0.001), and serum creatinine at last follow up (median 2.3mg/dL vs 1.56mg/dL, P=0.003). Cardiovascular disease, in addition to infection, is an important cause of death during the first 15 years following renal transplantation even in nondiabetic recipients. Death with functioning graft is of concern.

Spectrum of intradialytic complications during hemodialysis and its management: a single-center experience.

Hemodialysis (HD) is one of the important modalities of renal replacement therapy in acute renal failure (ARF) as well as chronic renal failure (CRF). This study was performed to evaluate the various intradialytic complications that occur during HD and their management. This is a retrospective study performed in patients who underwent conventional HD during the period of 1 January 2000 to 31 December 2011 at our center. Clinical details, various complications faced and their management were retrieved from dialysis case sheets. A total of 2325 patients of renal failure (790 ARF and 1535 CRF patients) were assessed for the intradialytic complications of HD. During the study period, there were 12,785 bicarbonate dialyses performed on these patients. In the ARF patients, the common intradialytic complications were: Hypotension, seen in 1296 sessions (30.4%), nausea and vomiting seen in 1125 sessions (26.4%), fever and chills seen in 818 sessions (19.2%), headache seen in 665 sessions (15.6%), cramps seen in 85 sessions (2.0%), chest pain and back pain seen in 82 sessions (1.92%), hypoglycemia seen in 77 sessions (1.8%), first-use syndrome seen in 72 sessions (1.7%) and femoral hematoma seen in 31 sessions (0.73%). In the CRF group, common complications were hypotension in 2230 sessions (26.1%), nausea and vomiting in 1211 sessions (14.2%), fever and chills in 1228 sessions (14.4%), chest pain and back pain in 1108 cases (13.0%), hypertension in 886 sessions (10.4%), headache in 886 sessions (10.4%), cramps in 256 sessions (3.0%), hematoma in 55 sessions (0.64%), intracerebral hemorrhage in three sessions (0.03%) and catheter tip migration in three sessions (0.03%). There is a need for special attention for the diagnosis and management of intradialytic complications of HD because such complications could be managed successfully without the need for termination of the dialysis procedure.

The high prevalence of chronic kidney disease-mineral bone disorders: A hospital-based cross-sectional study

Mineral bone disorder (MBD) is an important complication of chronic kidney disease (CKD). However, there are limited data on the pattern of MBD in Indian CKD population. The aim of this study was to describe spectrum of MBD in patients with CKD in our center. This was a hospital-based cross-sectional observational study. Patients with stage 4 and 5 CKD were included in this study. Those receiving calcium supplement, vitamin D or its analogues, and calcimimetic were excluded. Serum/plasma levels of creatinine, albumin, calcium, phosphate, total alkaline phosphatase (TAP), intact parathormone (iPTH), and 25-OH vitaminD (25-vitD) were measured. Radiological survey of bones was carried out in all cases, and echocardiography done in selected patients. Statistical analysis was done using Sigmaplot 10.0 software. A total of 150 patients (114 males, 36 females) were included in this study. Mean age was 45.67±16.96 years. CKD stage 4 and 5D were found in 26% (n=39) and 74% (n=111) of study population, respectively. The most common underlying native kidney diseases in patients of CKD 4 and 5D were diabetic nephropathy (41.03%) and CGN (41.44%), respectively. Median (first quartile, third quartile) values for serum levels of corrected calcium (cCa), phosphate, cCaXPO4 product, TAP, plasma iPTH, and 25-vitD in stage 4 CKD were 8.36 (7.79, 8.91) mg/dL, 4.9 (3.92, 6.4) mg/dL, 41.11 (34.01, 53.81) mg2/dL2, 97 (76.5, 184.25) IU/L, 231 (124.5, 430.75) pg/mL, and 12 (6.98, 23.55) ng/mL, respectively; and in stage 5D CKD were 8.36 (7.66, 8.95) mg/dL, 5.7 (4.23, 6.95) mg/dL, 46.5 (37.16, 54.47) mg2/dL2, 180 (114.5, 276.25) IU/L, 288 (169.75, 625.0) pg/mL, and 18.4 (10.0, 26.4) ng/mL, respectively. Prevalence of hypocalcemia (56.41% vs. 54.95%), hyperphosphatemia (64.10% vs. 70.27%), and hyperparathyroidism (84.62% vs. 88.29%) was not different between patients with CKD 4 and 5D. However, iPTH level outside the target range and increased TAP level were significantly (P<0.001) more common in CKD stage 5D. Multiple logistic regression analysis for hyperparathyroidism revealed significant inverse correlation with cCa in CKD 5D. There were no significant differences in vitamin D status and prevalence of valvular calcification between CKD stage 4 and 5D. X-ray revealed renal osteodystrophy in 8 (5.33%) patients, while it was normal in 118 (78.67%) patients. Secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, increased TAP, and 25-OH vitamin D deficiency and insufficiency were quite common in CKD 4 and 5 patients. The commonest type of MBD in CKD 4 and 5D was secondary hyperparathyroidism.

Insulin resistance in predialytic, nondiabetic, chronic kidney disease patients: A hospital-based study in Eastern Uttar Pradesh, India

Most investigations have focused on patients with end-stage renal disease (ESRD). More recently, due to increased recognition of the high prevalence of moderate-to-severe chronic kidney disease (CKD), attention has been redirected to this patient population to identify risk factors associated with hospitalization, death, and progression to ESRD. The objective of this study was to examine the degree and determinants of insulin resistance (IR) in predialytic, nondiabetic, CKD patients. Our study is a hospital-based cross-sectional study. The participants were aged 18 years and above with CKD due to any cause, were all nondiabetic patients, and the mean serum creatinine was 1.41-5 mg/dL. Anthropometric parameters included body weight, height, and skinfold thickness. Homeostasis model assessment of IR (HOMA-IR) score was 2.5 ± 1.2 in CKD patients and 1.9 ± 0.7 in controls. In the unadjusted analysis, there was a significant (P <0.05) correlation between HOMA-IR and body mass index (BMI), waist circumference, cholesterol, and triglyceride (TG) levels. Upon adjusting for age and sex, total body fat (BF), globulin, TG, and C-reactive protein were having positive, significant (P <0.05) correlation with HOMA-IR. In multivariate regression models, BMI and total BF% were significant (P <0.05) predictors of IR in patients with CKD but not in controls. BF% and BMI are indicators of IR in CKD as in non-CKD population.

Variation of body fat percentage with special reference to diet modification in patients with chronic kidney disease: A longitudinal study

Visceral adiposity causes hypertension, hyperglycemia and dyslipidemia. This study was conducted to evaluate whether a correlation exists between body fat percentage (BFP) of chronic kidney disease (CKD) patients and their dietary intake. In this hospital-based, quasi-experimental study, 135 incident cases of CKD were included, of whom 76 completed the study. The patients included were aged 18 years and above and had a body mass index (BMI) between 18 and 25 kg/m [2] , had CKD of any etiology and serum creatinine of up to 5 mg/dL. Patients with acquired immunodeficiency syndrome, active hepatitis B or C, malignancy, previous kidney transplantation, current participation in any trial, diabetes mellitus and those who were on dia-lysis were excluded. The study patients were put on a diet of 25-30 kcal/kg/day, with 60% of the calories coming from carbohydrates and 20% each from protein and fat. Assessment was made at baseline (BL) and at 12 months (TM) for anthropometric parameters, skin-fold thickness, nutritional parameters, serum albumin and dietary intake (3-day dietary record) and clinical characteristics. No significant change was seen in BFP, waist circumference (WC) and BMI at BS and at TM. There was significant improvement in serum albumin (P <0.05) and e-GFR (P <0.01) while CRP was elevated both at BL and TM. The dietary intake was within the prescribed limit, with significant improvement in energy intake between BS and TM (P <0.05). The intake of delta dietary protein and fat positively correlated with delta e-GFR (P <0.001). There was a significant association between change in BFP and change in BMI (P <0.005). During follow-up, there was no significant change in biochemical parameters and BFP as well as stage of CKD of the study patients. This study supports the fact that dietary counseling is an important part of treatment in patients with CKD.

Clinicopathologic spectrum of crescentic glomerulonephritis: a hospital-based study.

Recent data regarding the clinical and histopathologic spectrum of crescentic glomerulonephritis (CSGN) among the Indian adult population is unknown. Our aim is to study the clinicopathological features and outcome of CSGN. It is a retrospective observational study from a tertiary care hospital in India over 3.5 years. Biopsy-proven cases of CSGN (i.e., >50% crescents in glomeruli) were included in the study. Cases with insufficient data were excluded. There were 34 cases of CSGN, accounting for an incidence of 5.5% among kidney biopsies. The mean age was 32.2 ± 16.09 years, with male to female ratio of 12:22. Clinical presentations of CSGN include rapidly progressive glomerulonephritis in 23 (67.7%), chronic renal failure (CRF) in seven (20.5%), nephrotic syndrome in two (5.8%) and acute nephritic syndrome in two (5.8%) patients. The immunological profile of CSGN showed MPO-ANCA in nine (26.4%), PR3-ANCA in one (2.9%), both PR3 and MPO-ANCA in one (2.9%), anti-GBM antibody in five (14.7%) and lupus nephritis in six (17.6%) patients. All the three antibodies were present in one patient. The percentage of glomeruli showing crescents were 100% in nine (26.4%) and ≥80% in seven (20.5%) patients. Type of crescents seen were cellular in 11 (32.3%) and fibrocellular in 22 (64.7%) patients and fibrous in one (2.9%) patient. Interstitial fibrosis was found in seven (20.5%) patients. Dialysis dependency was seen in 11 (32.3%) patients. After 3 months of follow-up, mortality was seen in three (8.8%), remission in eight (23.5%), CRF in 15 (44.1%) and ESRD in five (14.7%) patients. CSGN carries a poor prognosis. The disorder may have an insidious onset and a slowly progressive course. ANCA, anti-GBM-antibody and anti-dsDNA can coexist in CSGN.

Renal cortical necrosis in a live kidney donor

Renal cortical necrosis (RCN) is a rare cause of acute renal failure (ARF). There is no clinical case report of RCN in a live kidney donor. A 48-year-old female kidney donor developed sudden anuria five hours postnephrectomy and remained anuric for more than three months on maintenance hemodialysis. Laboratory investigations revealed the features of hemolytic uremic syndrome. Contrast-enhanced computed tomography scan of abdomen showed hypoattenuated subcapsular rim of renal cortex favoring diagnosis of RCN. To the best of our knowledge, this is the first clinical case report of RCN in a live kidney donor in world literature.

Testing an association between TLR4 and CXCR1 gene polymorphisms with susceptibility to urinary tract infection in type 2 diabetes in north Indian population

BACKGROUND Genetic variations of Toll like receptor 4 (TLR4) and CXC-chemokine receptor type1 (CXCR1), the key elements of innate immune system and their association with urinary tract infection (UTI) were studied in general population. In present study we investigate genetic variation of these genes in diabetic patients (3 to 4 times higher prevalence of UTI in comparison to general population). METHODS A total 1100 subjects (318 diabetic patients with UTI, 324 diabetic patients without UTI, 200 non-diabetic UTI patients and 260 age matched healthy control) were enrolled in the study. SNPs of TLR4 rs4986790, rs4986791 and CXCR1 rs2234671 was assessed by PCR-RFLP and PCR-SSP respectively. RESULTS Statistical analysis revealed that A/G genotype and G allele of TLR4 rs4986790 are significantly associated with UTI in both diabetics and nondiabetic patients in comparison to healthy control. Similarly CT genotype and T allele of TLR4 rs4986791 are also significantly associated with UTI in both groups. We also found that prevalence of A/G genotype of TLR4 rs4986790 and CT genotype of TLR4 rs4986791 are significantly higher in patients of diabetes with UTI in comparison to diabetic patients without UTI. We did not find any association of CXCR1 rs2234671 polymorphism with UTI by comparing with any group. CONCLUSION We found that TLR4 rs4986790 and rs4986791 gene polymorphism is a risk for UTI development in both diabetic and nondiabetic patients in north Indian population.

Norepinephrine augmented in vitro growth of uropathogenic E. coli in Type 2 diabetes mellitus and its suppression by silodosin (alpha blocker)

Norepinephrine is secreted under conditions of stress in humans. The ability of bacteria to sense mammalian hormone may have a role in propagation of infection. The present study investigated the effect of norepinephrine on in vitro growth of uropathogenic E. coli (UPEC) and the effect of silodosin on norepinephrine-induced changes. The spot urine samples were collected from 56 individuals (14 diabetic patients with UTI, 14 diabetic without UTI, 14 non-diabetic UTI and 14 healthy volunteer controls) for the measurement of urinary norepinephrine concentrations. The concentration of norepinephrine, as found in urine of human subjects, was reproduced in artificial urine medium to study the growth of UPEC. The norepinephrine concentration showing maximum growth response was selected to study the effect of silodosin on the growth inhibition of UPEC. Result showed significantly elevated urinary norepinephrine in diabetic patients with and without UTI and also in nondiabetic UTI groups. The norepinephrine concentration equivalent to that in diabetic UTI patients enhanced the growth of UPEC. Furthermore, silodosin (0.32 μM) inhibited the growth of the UPEC.

Histopathological study of lupus nephritis with special reference to nonlupus nephritis, focal segmental glomerulosclerosis, interstitial nephritis, and amyloidosis

Context: Lupus nephritis (LN) is the involvement of kidney in systemic lupus erythematosus (SLE) where various types of glomerulonephritis (GN) are seen which affects the therapy also. Aims: To find out the frequency of various types of LN and nonlupus lesion in the kidney of SLE patient. Settings and Design: Retrospective analysis. Subjects and Methods: Total 52 cases of LN were studied between the periods of January 2011 and June 2014. Statistical Analysis Used: Calculation of mean and standard deviation. Results: There was female (76.93%) predominance over males (23.08%). In 63.46%, both ANA and dsDNA antibodies were positive. Only 57.69% patient had typical features of SLE and 17.29% patient had only one clinical manifestation to suggest SLE. In rest cases, renal limited SLE with severe anemia was found. Type IV LN was more common (53.84%) while Type III LN, Type II LN, and Type V LN were seen in equal frequency (9.61% each). In 2 cases, a combination of Type V + IV was found. In 5 cases (9.61%), nonlupus type of lesion was seen. It included 2 cases (3.84%) of amyloidosis and 3 cases of severe chronic tubulointerstitial nephritis with focal segmental glomerulosclerosis (5.76% FSGS). Out of 28 cases of Type IV LN, crescentic GN was found in 10 cases (19.23% CGN). In another 44.44% cases, focal crescents were seen in <40% glomeruli. Conclusions: Thus our study concludes that in LN Type IV is the most common LN and nonlupus related lesions, e.g., amyloidosis, and chronic interstitial nephritis and FSGS can also be found in LN.