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Biomedical subjects

Jai Radhakrishnan

Publications and source records attributed to Jai Radhakrishnan.

At least 19 recordsLinked to original sources
PubMed2026

Precision Diagnosis in APOL1 Kidney Disease With the p.N264K M1 Protective Variant.

IMPORTANCE: The APOL1 M1 (p.N264K) variant protects against G2-associated APOL1 focal segmental glomerulosclerosis (FSGS) and chronic kidney disease (CKD). However, the utility of knowing an individual's M1 status in guiding kidney disease diagnosis and other clinical scenarios remains underexplored. OBJECTIVE: To test 2 hypotheses: (1) in patients with APOL1 high-risk (HR) genotype kidney disease with at least 1 G2 allele, M1 can distinguish APOL1 CKD from non-APOL1 CKD; (2) in people with APOL1 low-risk (LR) genotypes, M1 is independently associated with protection against FSGS and CKD. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case-control study using data from 2 tertiary care hospitals (Columbia University Irving Medical Center and Mass General Brigham Biobank) and population-based data (the UK Biobank [UKB], Electronic Medical Records and Genomics [eMERGE-III], and All of Us [AoU]). Participants were individuals with a diagnosis of FSGS or steroid-resistant nephrotic syndrome (SRNS), individuals with CKD, and controls. EXPOSURES: Exposures included the M1 variant (p.N264K) obtained from exome or genome sequencing data, sex, and genetic ancestry. MAIN OUTCOME AND MEASURE: The main outcome was the presence or absence of kidney disease, defined as FSGS or non-FSGS CKD, compared with non-kidney disease controls. Association between the M1 variant and disease status was assessed using odds ratios (ORs). RESULTS: A total of 107 696 individuals (54 994 [51.1%] female; 8779 [8.2%] with African ancestry, 78 475 [72.9%] with European ancestry, and 16 129 [15.0%] with multiethnic ancestry), including 3460 with FSGS or SRNS, 24 382 with non-FSGS CKD kidney disease, and 79 854 controls were enrolled in the discovery cohort. In the APOL1-HR group (1413 participants), M1 was significantly inversely associated with FSGS or SRNS cases compared with controls without kidney disease (OR, 0.20; 95% CI, 0.04-0.63; P = 3.69 × 10-3). Among individuals with CKD with APOL1-HR genotypes, M1 was 4 times more frequent in those whose CKD was not due to FSGS or SRNS. Importantly, electronic health record and biopsy review identified an alternative, non-APOL1 cause for CKD in nearly all APOL1-HR-M1 cases. There was no association between individuals with APOL1-LR genotypes with M1 and protection against CKD or FSGS. CONCLUSIONS AND RELEVANCE: In this case-control study of 107 696 individuals, presence of an APOL1-HR genotype M1 was significantly associated with protection against kidney disease, suggesting that it may have a role as a genetic modifier. Patients with CKD with an APOL1-HR genotype and M1 should be evaluated for an alternative and potentially treatable cause of their CKD.

Humans↗
PubMed2005

Race/ethnicity, poverty status, and renal transplant outcomes.

BACKGROUND: There are known racial disparities in renal graft survival. Data are lacking comparing associations of race/ethnicity and socioeconomic status with graft failure and functional status after transplantation. Our goal was to test if African-American and Hispanic race/ethnicity and poverty are associated with worse outcomes following renal transplantation. METHODS: We performed a retrospective cohort study using a nationwide registry (United Network for Organ Sharing). We studied 4,471 adults who received renal transplants in 1990. Outcomes were graft failure and functional status over 10 years. RESULTS: Cumulative incidence of graft failure was higher among African-Americans and Hispanics than whites (77% vs. 64% vs. 60 %; P<0.001) and among transplant recipients living in the poorest areas (70% vs. 58% in the richest; P<0.001). African-American and Hispanic race/ethnicity were independently predictive of graft failure (RR 1.8, 95% CI 1.6-1.9; RR 1.3, 95% CI 1.2-1.6, respectively) in multivariate analyses but poverty status was not (RR 1.0, 95% CI 0.9-1.1). Days with impaired functional status were higher for African-Americans compared to whites (RR 1.6, 95% CI 1.3-1.9) but not independent of poverty. Poverty was independently associated with impaired functional status (RR 1.3, 95% CI 1.0-1.6). CONCLUSIONS: African-Americans and Hispanics had higher rates of graft failure compared to whites after adjustment for poverty and other covariates whereas poverty, but not race/ethnicity, was related to functional status following renal transplantation. National datasets should include individual-level measures of socioeconomic status in order to improve evaluation of social and environmental causes of disparities in renal transplant outcomes.

Adult↗
PubMed2005

Use of mycophenolate mofetil in autoimmune and renal diseases.

Progress in understanding the pathogenesis and treatment of rheumatologic and glomerular diseases such as systemic lupus erythematosus and particularly lupus nephritis has been closely linked with the development of newer immunosuppressive agents. With improved patient survival following the institution of cyclophosphamide and corticosteroid therapy, longer-term management issues came to the forefront, especially how to decrease adverse effects of the immunosuppressive regimen. Many of the immunosuppressive regimens used in lupus patients were first established as efficacious and safe through their use in solid organ transplantation. Mycophenolate mofetil (MMF) is now widely used in the field of transplantation. Following anecdotal reports describing benefits of MMF in lupus and lupus nephritis patients, small studies and finally large randomized, controlled trials have established the use of MMF in these patients, particularly those with lupus nephritis. MMF use in other rheumatologic and renal diseases has been evaluated in only smaller studies and very few randomized controlled trials. Nevertheless, many studies currently are ongoing with this immunosuppressive agent. This article will review the published data and the experience of two major New York medical centers with the use of MMF in autoimmune and renal diseases.

Acute Disease↗
PubMed2005

Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure.

The findings of diffuse tubular injury with abundant tubular calcium phosphate deposits on renal biopsy are referred to as nephrocalcinosis, a condition typically associated with hypercalcemia. During the period from 2000 to 2004, 31 cases of nephrocalcinosis were identified among the 7349 native renal biopsies processed at Columbia University. Among the 31 patients, 21 presented with acute renal failure (ARF), were normocalcemic, and had a history of recent colonoscopy preceded by bowel cleansing with oral sodium phosphate solution (OSPS) or Visicol. Because the precipitant was OSPS rather than hypercalcemia, these cases are best termed acute phosphate nephropathy. The cohort of 21 patients with APhN was predominantly female (81.0%) and white (81.0%), with a mean age of 64.0 yr. Sixteen of the 21 patients had a history of hypertension, 14 (87.5%) of whom were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The mean baseline serum creatinine was 1.0 mg/dl, available within 4 mo of colonoscopy in 19 (90.5%) patients. Patients presented with ARF and a mean creatinine of 3.9 mg/dl at a median of 1 mo after colonoscopy. In a few patients, ARF was discovered within 3 d of colonoscopy, at which time hyperphosphatemia was documented. Patients had minimal proteinuria, normocalcemia, and bland urinary sediment. At follow-up (mean 16.7 mo), four patients had gone on to require permanent hemodialysis. The remaining 17 patients all have developed chronic renal insufficiency (mean serum creatinine, 2.4 mg/dl). Acute phosphate nephropathy is an underrecognized cause of acute and chronic renal failure. Potential etiologic factors include inadequate hydration (while receiving OSPS), increased patient age, a history of hypertension, and concurrent use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

Acute Kidney Injury↗
PubMed2005

Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial.

BACKGROUND: IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. Up to 40% progress to end-stage renal disease (ESRD) over 10-20 years. Currently, treatment is limited. We studied the use of mycophenolate mofetil (MMF) vs placebo in a group of North American IgAN patients at high risk for progressive disease. METHODS: Included were 32 patients aged 18-75 years from multiple centres who had their biopsies read at Columbia and who had at least 1 g of proteinuria per day plus at least two of the following risk factors: (i) male sex; (ii) hypertension >150/90 mmHg or requiring antihypertensive medications; (iii) creatinine clearance, measured by 24 h urine collection, <80 and >20 ml/min at time of enrolment; and (iv) presence of glomerulosclerosis or tubulointerstitial atrophy and fibrosis on renal biopsy. Patients were randomized to either 1 year of MMF, titrated up to a dose of 1000 mg bid, or placebo. Total follow-up was 2 years. All patients received angiotensin inhibition medication. The primary outcome was a 50% increase in baseline serum creatinine (SCr). Secondary outcomes were an increase of 0.5 mg/dl SCr, ESRD and a 50% reduction in proteinuria. RESULTS: The mean baseline SCr was 2.4 mg/dl. No statistically significant differences were observed for any outcome. Five of 17 who received MMF vs two of 15 patients in the placebo group reached a 50% increase in SCr (P = 0.4). In both groups, all patients who reached the primary outcome also reached ESRD. Ten who received MMF vs seven who received placebo had a 0.5 mg/dl increase in SCr (P = 0.7) Only three MMF and two placebo patients had a 50% reduction in 24 h proteinuria. No serious adverse events occurred in either group. CONCLUSION: No benefit was seen in patients who received MMF in this high risk group, probably reflecting the relatively advanced stage of disease of our population. We conclude that MMF is probably not effective in patients with IgAN who already have moderate renal insufficiency.

Adult↗
PubMed2004

Renal failure due to acute nephrocalcinosis following oral sodium phosphate bowel cleansing.

Nephrocalcinosis is a chronic tubulointerstitial nephropathy characterized by tubular calcium phosphate deposition and slowly progressive renal insufficiency. We report a novel association of acute nephrocalcinosis and acute renal failure (ARF) with colonoscopy preceded by a bowel-cleansing regimen consisting of oral sodium phosphate solution (OSPS). A cohort of 5 patients (mean age, 69.2 years) had normal renal function (mean serum creatininem 0.9 mg/dL) before colonoscopy and presented with ARF (mean serum creatinine, 4.9 mg/dL) from 3 days to 2 months postcolonoscopy. Past medical history included hypertension in all 5 patients. Medications included an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) or angiotensin receptor blocker (ARB) in 4 patients and diuretics in 2 patients. In all patients, colonoscopy was preceded by bowel cleansing with OSPS; OSPS was contraindicated in a single patient with hyperparathyroidism and was used at excessive doses in another. Renal biopsy specimens obtained from all 5 patients revealed diffuse tubular injury and abundant tubular deposition of calcium phosphate. Although the tubular injury involved all tubular segments, lectin and immunohistochemical staining disclosed calcium phosphate deposition confined to distal tubules and collecting ducts. At a mean of 5.8 weeks of postbiopsy follow-up, renal function was unchanged in 4 patients and mildly improved in 1 patient. We conclude that acute nephrocalcinosis is a seemingly rare complication of bowel cleansing with OSPS. The pathophysiology of acute nephrocalcinosis after treatment with OSPS likely involves transient hyperphosphatemia; volume depletion exacerbated by intercurrent ACE-I, ARB, and diuretic use; and elevated distal tubular phosphate and calcium concentrations. Greater awareness of this entity is needed to identify potential risk factors.

Administration, Oral↗
PubMed2004

Awareness of kidney disease in the US population: findings from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000.

BACKGROUND: The prevalence of end-stage renal disease (ESRD) in the US population has been predicted to increase by 48% during the next decade and will pose a significant health cost burden. Early identification and treatment of chronic kidney disease (CKD) is necessary to delay progression from CKD to ESRD. CKD awareness among patients is crucial to early intervention programs, but its prevalence and characteristics in the noninstitutionalized US population are unknown. METHODS: The National Health and Nutrition Examination Survey 1999 to 2000 was used to determine prevalence estimates of kidney disease awareness, as well as demographics, health care access, and comorbid characteristics, of participants with CKD. RESULTS: In participants with CKD, 40.5% of patients with stage 1, 29.3% of patients with stage 2, 22.0% of patients with stage 3, and 44.5% of patients with stage 4 CKD were aware of their kidney disease, respectively. The aware and unaware groups did not differ by health care access. In multivariate regression modeling, lack of awareness was significantly associated with sex, race-ethnicity distribution, and hypertension. CONCLUSION: Kidney disease awareness is low among a representative sample of the noninstitutionalized US population. Groups at greater risk for kidney disease, such as non-Hispanic blacks, patients with hypertension, and men, were more likely to be unaware of having kidney disease, even with health care access similar to that of the aware group. Increased efforts to promote kidney disease awareness are needed and probably should target primary care providers involved in the screening process.

Adult↗
PubMed2003

Hyperlipidemia and thrombotic complications in patients with membranous nephropathy.

Membranous nephropathy (MN), the most common cause of adult-onset nephrotic syndrome (NS) in Caucasians, is associated commonly with the secondary complications of hyperlipidemia and hypercoagulability. These may increase the risk for cardiovascular disease, alter the rate of progression of renal disease, and raise the risk for thromboembolic events. The treatment of these secondary effects remains controversial. Although no clear practice guidelines are available to assist the clinician in deciding how and when to start disease-modifying therapies, the literature provides enough information to make reasonable decisions in most clinical scenarios. Prospective trials in the future will provide definitive information on how to best treat these abnormalities.

Anticoagulants↗
PubMed2003

Toxic acute tubular necrosis following treatment with zoledronate (Zometa).

BACKGROUND: Renal failure and toxic acute tubular necrosis (ATN) may be seen following exposure to a variety of therapeutic agents. Zoledronate (Zometa) is a new, highly potent bisphosphonate used in the treatment of hypercalcemia of malignancy. We report the first clinical-pathologic study of nephrotoxicity associated with this agent. METHODS: A cohort of six patients (four males and two females) with a mean age of 69.2 years received bisphosphonate therapy for multiple myeloma (five patients) or Paget's disease (one patient). In all patients, zoledronate was administered at a dose of 4 mg intravenously monthly, infused over at least 15 minutes, and the duration of therapy was mean 4.7 months (range, 3 to 9 months). RESULTS: All patients developed renal failure with a rise in serum creatinine from a mean baseline level of 1.4 mg/dL to 3.4 mg/dL. Renal biopsy revealed toxic ATN, characterized by tubular cell degeneration, loss of brush border, and apoptosis. Immunohistochemical staining revealed a marked increase in cell cycle-engaged cells (Ki-67 positive) and derangement in tubular Na+,K+-ATPase expression. Importantly, although all patients had been treated with pamidronate prior to zoledronate, no biopsy exhibited the characteristic pattern of collapsing focal segmental glomerulosclerosis observed in pamidronate nephrotoxicity. Following renal biopsy, treatment with zoledronate was discontinued and all six patients had a subsequent improvement in renal function (mean final serum creatinine, 2.3 mg/dL at 1 to 4 months of follow-up). CONCLUSION: The close temporal relationship between zoledronate administration and the onset of renal failure and the partial recovery of renal function following drug withdrawal strongly implicate this important and widely used agent in the development of toxic ATN.

Aged↗
PubMed2003

Prognosis in proliferative lupus nephritis: the role of socio-economic status and race/ethnicity.

BACKGROUND: Studies of proliferative lupus nephritis (PLN) suggest that African-Americans have a poorer prognosis than Whites. However, no study has simultaneously examined socio-economic status. We studied rates of progression of PLN among a tri-ethnic population with respect to socio-economic status and race/ethnicity. METHODS: A retrospective cohort study was carried out using individual and census-based neighbourhood data. Consecutive patients in urban tertiary care centres with biopsy-proven PLN were studied. The main outcome was time to doubling of serum creatinine. RESULTS: Among 128 patients with PLN, the percentage of patients who did not double their serum creatinine at 5 years was 67.0% (+/-4.8%) and at 10 years was 58.9% (+/-5.7%). In bivariate analyses, residence in a poor neighbourhood was positively associated with progression (P = 0.03), as was African-American and Hispanic race/ethnicity (P = 0.01). Residence in a poor neighbourhood remained associated with progression of disease after adjustment for age, sex, creatinine, hypertension, cyclophosphamide treatment and race/ethnicity [relative risk (RR) 3.5, 95% confidence interval (CI) 1.2-11, P = 0.03]. After adjustment for poverty and insurance, the RR for African-American race/ethnicity was reduced from 3.5 to 2.7 and was not statistically associated with progression of disease in the full model (P = 0.10). A similar reduction in RR from 5.5 to 3.6 was seen for Hispanic race/ethnicity, but this retained statistical significance (P = 0.03). CONCLUSIONS: Poverty is an important risk factor for progression of PLN, independent of race/ethnicity. Hispanics have an elevated risk similar to or greater than African-Americans. Given these findings, some of the poorer prognosis of African-American patients with PLN may result from socio-economic rather than biological or genetic factors.

Adolescent↗
PubMed2003

Analysis of metabolic parameters as predictors of risk in the RENAAL study.

OBJECTIVE: Metabolic factors such as glycemic control, hyperlipidemia, and hyperkalemia are important considerations in the treatment of patients with type 2 diabetes and nephropathy. In the RENAAL (Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan) study, losartan reduced renal outcomes in the patient population. This post hoc analysis of the RENAAL study reports the effects of losartan on selected metabolic parameters and assesses the relationship between baseline values of metabolic parameters and the primary composite end point or end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: Glycemic control (HbA(1c)) and serum lipid, uric acid, and potassium levels were compared between the losartan and placebo groups over time, and baseline levels were correlated with the risk of reaching the primary composite end point (doubling of serum creatinine, ESRD, or death) or ESRD alone. RESULTS: Losartan did not adversely affect glycemic control or serum lipid levels. Losartan-treated patients had lower total (227.4 vs. 195.4 mg/dl) and LDL (142.2 vs. 111.7 mg/dl) cholesterol. Losartan was associated with a mean increase of up to 0.3 mEq/l in serum potassium levels; however, the rate of hyperkalemia-related discontinuation was similar between the placebo and losartan groups. Univariate analysis revealed that baseline total and LDL cholesterol and triglyceride levels were associated with increased risk of developing the primary composite end point. Similarly, total and LDL cholesterol were also associated with increased risk of developing ESRD. CONCLUSIONS: Overall, losartan was well tolerated by patients with type 2 diabetes and nephropathy and was associated with a favorable effect on the metabolic profile of this population.

Cholesterol↗
PubMed2002

Angiotensin converting enzyme inhibition in chronic allograft nephropathy.

BACKGROUND: Although angiotensin-converting enzyme inhibition has been shown to slow progression of chronic allograft nephropathy in animal models, no studies have examined its efficacy in humans. METHODS: We retrospectively analyzed 63 patients with biopsy-proven chronic allograft nephropathy who had > or =6 months dialysis-free follow-up at our institution. A total of 32 patients treated for > or =6 consecutive months with angiotensin-converting enzyme inhibition and/or angiotensin-receptor blocker (ARB) therapy (group 1) were compared with 31 patients not on these agents (group 2). RESULTS: Except for a higher incidence of hypertension (100 vs. 78%, P=0.005) in group 1, there were no significant differences in baseline clinical characteristics at time of biopsy. With a mean follow-up time of 27 months in both groups, 6 of 32 (19%) group 1 patients vs. 12 of 31 (39%) group 2 reached the primary endpoint of > or =50% increase in serum creatinine (P=0.10). Mean time to primary endpoint was 46.6 months in group 1 vs. 32.7 months in group 2 (P=0.07). Three of 32 (9%) of group 1 patients vs. 8 of 31 (26%) of group 2 returned to dialysis during this time (P=0.11). Significantly fewer patients in group 1 reached the combined secondary endpoint of allograft failure or death (9.4 vs. 35.5%, P=0.01); in addition, group 1 had a longer mean time to this endpoint (51.2 vs. 37.6 months, P=0.03). On multivariate analysis, the only predictor of progression to primary endpoint was a high baseline serum creatinine (P=0.02). No significant differences in hyperkalemia or anemia were found between the two groups. CONCLUSIONS: Angiotensin-converting enzyme inhibition/angiotensin-receptor blocker therapy is well tolerated in renal allograft recipients with chronic allograft nephropathy. It is associated with a trend of slowing renal insufficiency as well as a significant survival benefit in the combined endpoint of allograft failure or death.

Adult↗
PubMed2002

Thrombotic microangiopathies.

The thrombotic microangiopathies (TMA) are a group of diseases associated with microangiopathic hemolytic anemia, thrombocytopenia, and end-organ dysfunction. These seemingly disparate entities share in common a pathogenic mechanism involving endothelial injury and thrombus formation. Prognosis and treatment depend on the nature of the underlying disease.

Anemia, Hemolytic↗
PubMed2002

Fludarabine treatment of cryoglobulinemic glomerulonephritis.

Three patients (one hepatitis C positive) presented with renal insufficiency and nephrotic-range proteinuria resulting from mixed cryoglobulinemia and glomerulonephritis. All three patients received two to four cycles of intravenous fludarabine (each cycle consisted of 25 to 50 mg/d for 4 to 5 days). All patients responded to therapy with a decrease in proteinuria, increase in serum albumin, and decrease in serum creatinine. This response was evident by 2 months and persisted for 2 to 5 years. In two patients, this response was accompanied by disappearance of cryoglobulins, at least transiently. One patient developed tuberculosis with neutropenia. Transient blindness and neutropenia were seen in another patient. These results suggest that fludarabine may be a useful treatment in cryoglobulinemia with glomerulonephritis, although its use may be accompanied by side effects.

Adult↗