About

Nirupama Ramkumar, MD, MPH, is an Associate Professor of Internal Medicine at the University of Utah Health. She received her medical degree from Bangalore University, India, and obtained her Master's degree in Public Health from the University of Utah. Her clinical interests include hypertension, polycystic kidney disease, and chronic kidney disease. She completed her residency training in Internal Medicine at UCSF-Fresno and her Nephrology fellowship training at the University of Utah. Dr. Ramkumar oversees Nephrology fellows in training in both outpatient and inpatient settings. Her research focuses on various aspects of kidney health, including the molecular mechanisms of kidney injury, the role of renin and other signaling pathways in renal physiology, and potential therapeutic strategies for kidney diseases. She has contributed to numerous publications in the field of nephrology, emphasizing her active engagement in advancing kidney research.

Research topics

• Biology
• Endocrinology
• Medicine
• Internal medicine
• Bioinformatics
• Biochemistry
• Pharmacology
• Pathology
• Chemistry
• Immunology
• Molecular biology

Selected publications

• A High-fat, High-salt Diet Model of MDAKD Impairs Bioenergetic Efficiency for ATP Synthesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-22

  articleOpen access

  Metabolic dysfunction-associated kidney disease (MDAKD) is closely linked to dietary excess, but models that capture early kidney injury without obesity are limited. We fed male C57BL/6J (6J) and C57BL/6N (6N) mice a high-fat, high-sodium (HF/HNa) or control diet for 16 weeks. HF/HNa feeding did not alter body weight, adiposity, or total food intake; however, it increased dietary energy and sodium exposure, kidney mass, water intake, and urine volume. GFR declined modestly in 6J mice, whereas 6N mice maintained or slightly increased GFR. Both substrains showed increased urinary albumin, creatinine, KIM-1, and NGAL, while cystatin C rose predominantly in 6N mice, indicating strain-dependent tubular injury. Whole-kidney trichrome staining revealed increased fibrotic area with HF/HNa, particularly in 6N mice, without significant changes in glomerular morphology. In isolated renal mitochondria, oxygen consumption was preserved, but ATP production and ATP:O ratios were reduced, with unchanged citrate synthase activity and OXPHOS protein abundance, consistent with early mitochondrial bioenergetic uncoupling. Exploratory urinary proteomics in 6J mice identified HF/HNa-associated changes in proteins linked to tubular stress and extracellular matrix remodeling. These findings define an early MDAKD-like renal phenotype with strain-specific functional responses, tubular injury, fibrosis, and impaired mitochondrial ATP efficiency. Translational Statement: Metabolic Dysfunction-Associated Kidney Disease (MDAKD) is a leading driver of chronic kidney disease (CKD) in the world. In addition to obesity and related comorbidities, renal mitochondrial dysfunction is thought to be a key contributor to the development of CKD in patients with MDAKD; however, few models recapitulate the progression of MDAKD. We couple well-established mouse models of obesity, namely the C57Bl/6J and C57Bl/6N mouse lines, with a high-fat, high-salt diet to induce renal mitochondrial dysfunction, leading to early stages of MDAKD as indicated by widespread fibrosis and mild reduction in glomerular filtration rate, though these effects were strain-dependent. We identify diet-induced mitochondrial dysfunction as a common feature in both mouse strains, suggesting impairments in mitochondrial respiration and oxidative ATP production are indeed a contributing factor to the development of MDAKD. This study highlights the role of energetic impairments in the pathogenesis of MDAKD and may guide future therapies for CKD.

  PublisherOA PDFDOI

• Delineating the role of ceramides in kidney disease and fibrosis

  Physiology · 2026-05-01

  articleSenior author

  Background: Ceramides are bioactive lipid species that contribute to lipotoxicity and cell death. The rate limiting, first step in the ceramide biosynthesis pathway is catalyzed by serine palmitoyl transferase (SPT) comprising of 3 different subunits (SPTLC1, SPTLC2, SPTLC3). In this study, we examined whether kidney tubule specific SPT overexpression was sufficient to induce tubular injury in C57BL/6 mice. Methods: We generated a transgenic mouse with overexpression of a fused construct encoding a functional SPT heterodimer fSPT(SPTLC1, SPTLC2 and ssSPTa) selectively in the kidney tubules by crossing floxed fSPT mice with mice carrying the Pax8-rtTA/LC1 transgenes. Male and female floxed fSPT mice and fSPTOE mice were treated with doxycycline chow (600mg/kg) for 14 days at 8 weeks of age. Metabolic balance studies were performed at 10 and 20 weeks of age for urine collection. Kidneys were isolated to evaluate kidney injury and histology. Overexpression of kidney ceramides was confirmed with lipidomic analyses. Statistical analyses were performed using unpaired Student’s t-test. Results: Compared to floxed controls, fSPTOE mice had a 5.3-fold increase in Sptlc1 and Sptlc2 expression in the kidneys (p< 0.01, n=8-10 mice/group for males, n=2-4 mice for females). Lipidomic analyses of kidneys demonstrated that fSPTOE mice had 1.68 fold higher ceramides (Cer 18:1;O2/22:0: 53,664 ± 15319 vs floxed: 30,779 ± 8763 pmol/g, p< 0.001), 6.54 fold higher dihydroceramides (Cer 18:0;O2/22:0: 9122 ± 3510 vs floxed: 1395 ± 1188 pmol/g, p=0.001), 5.5 fold higher sphinganine (656 ± 578 vs floxed: 119 ± 44.2 pmol/g, p=0.01) and 1.77 fold higher sphingosine (6134 ±2817 vs floxed: 3464 ± 589 pmol/g, p< 0.01) relative to floxed controls. Despite similar food intake and body weight between the two groups, fSPTOE mice had increased water intake (8.0 ± 0.7 vs floxed 3.6 ± 1.6 ml/day, p=0.01) and urine volume (3.6 ± 0.6 vs floxed 1.2 ± 0.4 ml/day, p=0.04) at 20 weeks of age. Serum electrolytes were comparable between the two groups although blood urea nitrogen (floxed 29.2 ± 11.6 vs fSPTOE 79.2 ± 35.2 mg/dl, p=0.02) and creatinine (floxed 0.2 ± 0.01 vs fSPTOE 0.34 ± 0.1 mg/dl, p=0.02) were elevated. Compared to floxed controls, fSPTOEmice had 30.2 ± 22.2 fold increase in kidney Havcr1 expression (p< 0.01) without significant differences in kidney col1a1 and Fn1 expression. Kidney histology demonstrated moderate tubular injury with varying degrees of fibrosis by Trichrome staining in the fSPTOE mice. Male and female floxed and fSPTOE showed similar trends without any sex differences. Conclusion: Overexpression of SPT results in significant increase in kidney sphingolipids with evidence of tubular injury. Studies are currently ongoing to investigate whether overexpression of SPT exacerbates acute or chronic kidney disease. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Kidney Cysts and Uncontrolled Hypertension: A Dissecting Diagnosis

  Journal of the American Society of Nephrology · 2025-10-01

  articleSenior author

  Introduction: Autosomal dominant polycystic kidney disease (ADPKD), the most common genetic cause of kidney disease, is associated with cardiovascular complications. There are guidelines for screening for intracranial aneurysm (ICA), however, a paucity of research regarding the risk of extracranial aneurysms and other vascular abnormalities. Here we discuss the case of a young patient without known medical problems diagnosed simultaneously with aortic dissection and ADPKD. Case Description: A 30-year-old male presented to the ED with severe back pain. A CT scan revealed thoracic aortic abdominal dissection (TAAD) and massive enlargement of bilateral kidneys measuring 30cm and 26cm with a variety of cysts consistent with ADPKD. Of note, creatinine was 3.4 mg/dL and eGFR was 23 ml/min with unknown baseline. His blood pressure required 5 agents for control but he was in normal health prior to admission with no known medical issues. He was unaware of ADPKD diagnosis but his mom and two cousins have ADPKD and/or end-stage renal disease. During admission he underwent aortic repair and recovered well. His eGFR was 17 ml/min at the time of discharge but was unfortunately lost to follow up. Of note, our patient lacked many known risk factors of aortic dissection including hypertension, collagen disorders, or trauma but did report a history of cigarette smoking. Discussion: ADPKD is often caused by PKD1 and PKD2 genes and affects multiple organ systems. Notably the expression of PKD1 in vascular smooth muscle and PKD2 in endothelium creates risk factors for ICA, TAAD, and aortic root dilation. Our patient lacked risk factors of vascular dissection upon presentation, raising suspicion of association with his ADPKD. Studies have shown an increased risk of aortic dissection in patients with ADPKD, including a cohort study in Taiwan that found a 5-fold risk increase. This case brings to light the risks and benefits of preemptive screening for vascular anomalies beyond ICA in patients with ADPKD.

  PublisherDOI

• Therapeutic remodeling of the ceramide backbone prevents kidney injury

  Cell Metabolism · 2025-11-12 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Reduced Cardiolipin Drives Defects in ATP Production and May Contribute to Reduced GFR and CKD Progression

  Journal of the American Society of Nephrology · 2025-10-01

  article
  PublisherDOI

• N-acetylcarnosine attenuates age-associated declines in multi-organ systems to improve survival

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-22

  preprintOpen access

  Histidine containing dipeptides (HCDs) such as N-acetylcarnosine are endogenous metabolites that are ergogenic and mitigate metabolic dysfunction. We previously demonstrated that short-term N-acetylcarnosine treatment is highly efficacious in protecting muscle atrophy induced by disuse. Here we demonstrate that a 6-months treatment of N-acetylcarnosine attenuates a broad spectrum of age-associated maladies and improved survival by ~50% in female mice. A comprehensive survey of organ systems revealed that N-acetylcarnosine prevents decline in adiposity, diastolic function, vasodilation, muscle strength, and bone density. Together, N-acetylcarnosine substantially delays the onset of system-wide end-stage pathology to prolong lifespan. As an endogenously present metabolite, treatment with N-acetylcarnosine may be a safe and promising intervention to promote healthy aging in humans.

  PublisherOA PDFDOI

• A Diagnostic Challenge: Distinguishing Complement-Mediated and Hypertension-Induced Thrombotic Microangiopathy

  Journal of the American Society of Nephrology · 2025-10-01

  article

  Introduction: Thrombotic Microangiopathy (TMA) is a serious condition characterized by microangiopathic anemia, thrombocytopenia, and end organ damage. Prompt initiation of treatment for TMA is important in preventing irreversible damage, though tests can take multiple days to result and sometimes a clear diagnosis is not made. In particular, several articles have suggested links between malignant hypertension and genetic mutations in the complement pathway, making the distinction between the two very difficult. Case Description: A 39-year-old female presented with hypertensive emergency and was found to have acute kidney injury with creatinine of 12 mg/dl. Workup revealed hemolytic anemia, thrombocytopenia, proteinuria, and hematuria but broad serologic work-up was negative. She became oliguric and required dialysis shortly after admission. She had evidence of hypertensive damage including left ventricular hypertrophy and hypertensive retinopathy. The patient’s anemia, thrombocytopenia, and general symptoms improved with blood pressure control. Kidney biopsy was consistent with TMA with evidence of hypertensive damage including “onion skinning” and marked arteriosclerosis. Her renal function failed to improve despite adequate blood pressure management. Genetic testing revealed a heterozygous variant in C3AR1 gene, a variant of undetermined significant that has been associated with complement mediated TMA. She was started on eculizumab for potential complement mediated TMA. Discussion: The potential overlap in pathophysiology between complement mediated TMA and hypertension induced TMA is less recognized. Genetic abnormalities are not discovered in a significant proportion of cases of complement mediated TMA. Meanwhile, approximately 50% of cases of hypertension induced TMA reveal abnormalities in complement genes. Case reports have shown renal function improvement in cases of refractory hypertension induced TMA, even months after diagnosis, after eculizumab treatment. With the relatively efficacious treatment for complement mediated HUS with anti-complement therapy and the diagnostic ambiguity in these cases, the decision to initiate eculizumab therapy remains difficult. Fortunately, there is growing research into tests that may help identify patients that would benefit from eculizumab therapy.Fibrin Deposition and Luminal Occlusion

  PublisherDOI

• Role of the soluble (pro)renin receptor in obstruction induced chronic kidney disease

  Physiology · 2025-05-01

  articleSenior author

  Background: The (pro)renin receptor (PRR) is a multifunctional, transmembrane protein that is critical to nephron development and renal tubular function. In its cleaved form, the soluble (pro)renin receptor (sPRR) is important in blood pressure regulation and kidney function. We previously reported that loss of sPRR attenuated angiotensin-II induced hypertension and adenine induced kidney disease. In this study, we investigated whether loss of the sPRR is protective in obstructive chronic kidney disease (CKD). Methods: Using CRISP-Cas9, we developed a mouse model with site directed mutagenesis of the PRR cleavage site. Male, 5-7 month-old, mutant sPRR mice and littermate controls were subjected to sham or unilateral ureteral obstruction-release (UUOR) procedure. The UUOR procedure involved obstruction of the left ureter for 72 hours, followed by release and evaluation of kidney injury and fibrosis 28-days later. Obstructed kidney was examined for tubular injury (kidney injury marker-1, KIM-1) and fibrosis markers (collagen-I and fibronectin) using RT-PCR. Histology using Trichrome, PAS staining, and Sirius Red staining was used to assess kidney injury. GFR and BUN were also measured at the end of the study. Two-way ANOVA was used to examine differences among the groups. Results: Compared to controls, male mutant sPRR mice had markedly lower plasma sPRR levels (control: 24.4 ± 5.0 vs 0.3 ± 0.05 ng/ml, p value <0.001). Compared to control mice subjected to sham procedure (N=4), the control UUOR mice (N=6) had 5.3 ± 1.6 fold increase in collagen-I expression while the mutant UUOR mice (N=6) had 2.2 ± 0.5 fold increase; a 2.3 ± 0.3 fold increase in fibronectin while mutant UUOR had 1.5 ± 0.4 fold increase; and 66.4 ± 14.9 fold increase in KIM-1 while mutant UUOR 48.9 ± 20.1 fold increase (ANOVA p=0.05 by genotype & surgery, p<0.01 by fibrosis marker and interaction). Post-hoc analyses of multiple comparisons showed that control UUOR had higher KIM-1 compared to control sham (p<0.05) or mutant UUOR (p=0.05). Kidney histology by PAS and Trichrome staining showed increased inflammation and tubular damage in the control UUOR group compared to control sham and mutant sPRR mice. No differences in BUN or GFR were observed comparing sham versus UUOR in control or mutant sPRR mice which is expected as the contralateral kidney likely compensated for loss of kidney function in the obstructed kidney. Conclusion: The loss of the sPRR may be protective in mice with obstructive kidney disease. Further studies are planned to delineate the molecular mechanisms by which loss of sPRR affords kidney protection. R01DK133271 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Fast and Furious: IgAN with Rapidly Progressive Glomerulonephritis

  Journal of the American Society of Nephrology · 2025-10-01

  article

  Introduction: IgA Nephropathy (IgAN) is the most common cause of glomerulonephritis and can manifest with a wide range of kidney impairment, ranging from asymptomatic hematuria to Rapidly Progressive Glomerulonephritis (RPGN). This later entity is uncommon, encompassing <10% of IgAN presentations, and generally leads to poor renal outcomes. Despite the many recent advances in the field of IgAN management, the optimal management of IgAN with RPGN remains unclear and current guidelines recommend treating these patients with cyclophosphamide and glucocorticoids similar to patients with renal ANCA-associated vasculitis. Case Description: A 21-year-old man presented after a month of fevers, chills, pharyngitis, non-productive cough, edema, and lower extremity palpable purpura and was found to have AKI with nephrotic range proteinuria and hematuria. History was notable for an AKI with hematuria and proteinuria shortly after an episode of pharyngitis two years earlier, though repeat labs found normal renal function with bland urine soon after and he was later lost to follow up. On his current presentation serologic testing and renal imaging was unremarkable. Renal biopsy was obtained which showed findings of a crescentic glomerulonephritis with IgA dominant deposits. He received treatment with pulse dose steroids and cyclophosphamide. He required hemodialysis due to hypervolemia and hyperkalemia, and unfortunately has remained dialysis-dependent four months out from his presentation. Discussion: This case of IgAN with RPGN demonstrates the rapid development of kidney failure in a young patient despite prompt and intensive immunosuppression. The current recommendations for treatment of IgAN with RPGN are based on limited prospective data as there are no randomized controlled trials studying this entity. Ongoing research is needed to better inform management of this uncommon but devastating IgAN presentation.

  PublisherDOI

• Combined sedentarism and high-fat diet induce early signs of kidney injury in C57BL/6J mice

  American Journal of Physiology-Renal Physiology · 2025-05-06 · 3 citations

  articleOpen access

  Physical inactivity is a risk factor for chronic kidney disease. Our laboratory recently developed a new mouse model of physical inactivity (small mouse cage housing) that more closely recapitulates the metabolic disturbances that occur with sedentary behavior. In this paper, we performed an in-depth phenotyping of kidney function and metabolic parameters in response to small mouse cage housing.

  PublisherDOI

Frequent coauthors

• Donald E. Kohan

  University of Utah

  55 shared

• Taiji Matsusaka

  Tokai University

  51 shared

• Ewout J. Hoorn

  Erasmus University Rotterdam

  50 shared

• Kate M. Denton

  49 shared

• Jia L. Zhuo

  Tulane University

  49 shared

• Frank Geurts

  Erasmus MC

  49 shared

• A.H. Jan Danser

  Erasmus MC

  49 shared

• Hui Lin

  Second Hospital of Shanxi Medical University

  49 shared

Education

• M.D.

  Bangalore University

• M.A., Public Health

  University of Utah

• Other, Internal Medicine

  UCSF-Fresno

• Other, Nephrology

  University of Utah

Awards & honors

• American Society of Nephrology Kidney Tutored Research and E…