- Resistant Hypertension
- Diabtetic Kidney Disease
- Electrolyte Disorders
Honors & Awards
Fellow, American Society of Nephrology (2003)
Mentored Clinical Scientist Award, NIH/NIDDK (2005)
Teaching Awardee, Halie T. Debas Academy of Medical Educators, UCSF (2007)
Shaul G. Massry Young Investigators Award, National Kidney Foundation (2008)
Carl W. Gottschalk Research Grant, American Society of Nephrology (2010-2012)
Henry J Kaiser Family Foundation Award for Excellence in Preclinical Teaching, Stanford University School of Medicine (2012)
Boards, Advisory Committees, Professional Organizations
Biosciences Research Advisory Group, American Society of Nephrology (2014 - Present)
Board Certification, American Society of Hypertension, Clinical Hypertension (2015)
Board Certification: Nephrology, American Board of Internal Medicine (2003)
Board Certification: Internal Medicine, American Board of Internal Medicine (2001)
Fellowship:UCSF-Graduate Medical Education (2005) CA
Residency:Harbor-UCLA Medical Center (2001) CA
Medical Education:University of California San Diego (1998) CA
Fellowship, Univ of California San Francisco, Nephrology (2005)
Residency, Harbor-UCLA Medical Center, Internal Medicine (2001)
M.D., Univ of California San Diego, Medicine (1998)
B.S., Univ of California Berkeley, Electrical Engineering (1994)
Current Research and Scholarly Interests
Dr. Bhalla's research interests are in the pathogenesis of diabetic kidney disease and salt-sensitive hypertension. The laboratory is interested in elucidating regulators of inflammation in diabetic glomeruli. We interface these studies with collaborative projects on biomarkers for human diabetic nephropathy. We also study the mechanisms of aberrant sodium handling in the setting of obesity and insulin resistance. We use molecular and transgenic approaches to address our research questions.
Graduate and Fellowship Programs
- Harvest and primary culture of the murine aldosterone-sensitive distal nephron AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 2015; 308 (11): F1306-F1315
- Is there a sweet spot for Nrf2 activation in the treatment of diabetic kidney disease? Diabetes 2014; 63 (9): 2904-2905
Racial/Ethnic Differences in the Prevalence of Proteinuric and Nonproteinuric Diabetic Kidney Disease
2013; 36 (5): 1215-1221
OBJECTIVE To examine racial/ethnic differences in the prevalence of diabetic kidney disease (DKD), with and without proteinuria, in an outpatient health care organization. RESEARCH DESIGN AND METHODS We examined electronic health records for 15,683 persons of non-Hispanic white (NHW), Asian (Asian Indian, Chinese, and Filipino), Hispanic, and non-Hispanic black (NHB) race/ethnicity with type 2 diabetes and no prior history of kidney disease from 2008 to 2010. We directly standardized age- and sex-adjusted prevalence rates of proteinuric DKD (proteinuria with or without low estimated glomerular filtration rate [eGFR]) or nonproteinuric DKD (low eGFR alone). We calculated sex-specific odds ratios of DKD in racial/ethnic minorities (relative to NHWs) after adjustment for traditional DKD risk factors. RESULTS Racial/ethnic minorities had higher rates of proteinuric DKD than NHWs (24.8-37.9 vs. 24.8%) and lower rates of nonproteinuric DKD (6.3-9.8 vs. 11.7%). On adjusted analyses, Chinese (odds ratio 1.39 for women and 1.56 for men), Filipinos (1.57 for women and 1.85 for men), Hispanics (1.46 for women and 1.34 for men), and NHBs (1.50 for women) exhibited significantly (P < 0.01) higher odds of proteinuric DKD than NHWs. Conversely, Chinese, Hispanic, and NHB women and Hispanic men had significantly lower odds of nonproteinuric DKD than NHWs. CONCLUSIONS We found novel racial/ethnic differences in DKD among patients with type 2 diabetes. Racial/ethnic minorities were more likely to have proteinuric DKD and less likely to have nonproteinuric DKD. Future research should examine diverse DKD-related outcomes by race/ethnicity to inform targeted prevention and treatment efforts and to explore the etiology of these differences.
View details for DOI 10.2337/dc12-0951
View details for Web of Science ID 000319782100025
- A transcriptional blueprint for human and murine diabetic kidney disease. Diabetes 2013; 62 (1): 31-33
Low-Level Lead Exposure and the Prevalence of Gout An Observational Study
ANNALS OF INTERNAL MEDICINE
2012; 157 (4): 233-?
Blood lead levels (BLLs) less than 1.21 µmol/L (<25 µg/dL) among adults are considered acceptable by current national standards. Lead toxicity can lead to gouty arthritis (gout), but whether the low lead exposure in the contemporary general population confers risk for gout is not known.To determine whether BLLs within the range currently considered acceptable are associated with gout.Population-based cross-sectional study.The National Health and Nutrition Examination Survey for 2005 through 2008.6153 civilians aged 40 years or older with an estimated glomerular filtration rate greater than 10 mL/min per 1.73 m2.Outcome variables were self-reported physician diagnosis of gout and serum urate level. Blood lead level was the principal exposure variable. Additional data collected were anthropometric measures, blood pressure, dietary purine intake, medication use, medical history, and serum creatinine concentration.The prevalence of gout was 6.05% (95% CI, 4.49% to 7.62%) among patients in the highest BLL quartile (mean, 0.19 µmol/L [3.95 µg/dL]) compared with 1.76% (CI, 1.10% to 2.42%) among those in the lowest quartile (mean, 0.04 µmol/L [0.89 µg/dL]). Each doubling of BLL was associated with an unadjusted odds ratio of 1.74 (CI, 1.47 to 2.05) for gout and 1.25 (CI, 1.12 to 1.40) for hyperuricemia. After adjustment for renal function, diabetes, diuretic use, hypertension, race, body mass index, income, and education level, the highest BLL quartile was associated with a 3.6-fold higher risk for gout and a 1.9-fold higher risk for hyperuricemia compared with the lowest quartile.Blood lead level does not necessarily reflect the total body lead burden.Blood lead levels in the range currently considered acceptable are associated with increased prevalence of gout and hyperuricemia.
View details for Web of Science ID 000307813200014
View details for PubMedID 22910934
Neural Precursor Cell-expressed Developmentally Down-regulated Protein 4-2 (Nedd4-2) Regulation by 14-3-3 Protein Binding at Canonical Serum and Glucocorticoid Kinase 1 (SGK1) Phosphorylation Sites
JOURNAL OF BIOLOGICAL CHEMISTRY
2011; 286 (43): 37830-37840
Regulation of epithelial Na(+) channel (ENaC)-mediated transport in the distal nephron is a critical determinant of blood pressure in humans. Aldosterone via serum and glucocorticoid kinase 1 (SGK1) stimulates ENaC by phosphorylation of the E3 ubiquitin ligase Nedd4-2, which induces interaction with 14-3-3 proteins. However, the mechanisms of SGK1- and 14-3-3-mediated regulation of Nedd4-2 are unclear. There are three canonical SGK1 target sites on Nedd4-2 that overlap phosphorylation-dependent 14-3-3 interaction motifs. Two of these are termed "minor," and one is termed "major," based on weak or strong binding to 14-3-3 proteins, respectively. By mass spectrometry, we found that aldosterone significantly stimulates phosphorylation of a minor, relative to the major, 14-3-3 binding site on Nedd4-2. Phosphorylation-deficient minor site Nedd4-2 mutants bound less 14-3-3 than did wild-type (WT) Nedd4-2, and minor site Nedd4-2 mutations were sufficient to inhibit SGK1 stimulation of ENaC cell surface expression. As measured by pulse-chase and cycloheximide chase assays, a major binding site Nedd4-2 mutant had a shorter cellular half-life than WT Nedd4-2, but this property was not dependent on binding to 14-3-3. Additionally, a dimerization-deficient 14-3-3? mutant failed to bind Nedd4-2. We conclude that whereas phosphorylation at the Nedd4-2 major site is important for interaction with 14-3-3 dimers, minor site phosphorylation by SGK1 may be the relevant molecular switch that stabilizes Nedd4-2 interaction with 14-3-3 and thus promotes ENaC cell surface expression. We also propose that major site phosphorylation promotes cellular Nedd4-2 protein stability, which potentially represents a novel form of regulation for turnover of E3 ubiquitin ligases.
View details for DOI 10.1074/jbc.M111.293233
View details for Web of Science ID 000296542400077
View details for PubMedID 21900244
- In diabetic nephropathy, high doses of vitamin B decrease glomerular filtration rate and increase risk of the composite outcome of a vascular event or all-cause mortality compared with placebo. Evidence-based medicine 2011; 16 (1): 14-15
Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial
2010; 376 (9756): 1903-1909
Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension.In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more (≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group) at 24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00888433.106 (56%) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal denervation and 51 (94%) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment.Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients.Ardian.
View details for DOI 10.1016/S0140-6736(10)62039-9
View details for Web of Science ID 000285439800031
View details for PubMedID 21093036
Phosphopeptide Screen Uncovers Novel Phosphorylation Sites of Nedd4-2 That Potentiate Its Inhibition of the Epithelial Na+ Channel
JOURNAL OF BIOLOGICAL CHEMISTRY
2010; 285 (28): 21671-21678
The E3 ubiquitin ligase Nedd4-2 regulates several ion transport proteins, including the epithelial Na(+) channel (ENaC). Nedd4-2 decreases apical membrane expression and activity of ENaC. Although it is subject to tight hormonal control, the mechanistic basis of Nedd4-2 regulation remains poorly understood. To characterize regulatory inputs to Nedd4-2 function, we screened for novel sites of Nedd4-2 phosphorylation using tandem mass spectrometry. Three of seven identified Xenopus Nedd4-2 Ser/Thr phosphorylation sites corresponded to previously identified target sites for SGK1, whereas four were novel, including Ser-293, which matched the consensus for a MAPK target sequence. Further in vitro and in vivo phosphorylation experiments revealed that Nedd4-2 serves as a target of JNK1, but not of p38 MAPK or ERK1/2. Additional rounds of tandem mass spectrometry identified two other phosphorylated residues within Nedd4-2, including Thr-899, which is present within the catalytic domain. Nedd4-2 with mutations at these sites had markedly inhibited JNK1-dependent phosphorylation, virtually no ENaC inhibitory activity, and significantly reduced ubiquitin ligase activity. These data identify phosphorylatable residues that activate Nedd4-2 and may work together with residues targeted by inhibitory kinases (e.g. SGK1 and protein kinase A) to govern Nedd4-2 regulation of epithelial ion transport.
View details for DOI 10.1074/jbc.M109.084731
View details for Web of Science ID 000279516100054
View details for PubMedID 20466724
Lead poisoning from an Ayurvedic herbal medicine in a patient with chronic kidney disease
NATURE REVIEWS NEPHROLOGY
2009; 5 (5): 297-300
A 60-year-old man with a history of diabetes and hypertension was referred to a nephrology clinic for investigation of his elevated serum creatinine level.Physical examination; laboratory investigations, including measurement of whole-blood lead level, body lead burden and urine albumin:creatinine ratio; history of lead exposure and use of herbal medical products; and renal ultrasonography.Stage 3 chronic kidney disease that was probably worsened by consumption of lead in the form of an Ayurvedic herbal remedy.Cessation of the herbal product, followed by lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid. The patient's whole-body lead burden and blood lead level decreased to acceptable levels and his serum creatinine value was within the normal range at final follow-up.
View details for DOI 10.1038/nrneph.2009.41
View details for Web of Science ID 000265854500012
View details for PubMedID 19384331
Melamine nephrotoxicity: an emerging epidemic in an era of globalization
2009; 75 (8): 774-779
Recent outbreaks of nephrolithiasis and acute kidney injury among children in China have been linked to ingestion of milk-based infant formula contaminated with melamine. These cases provide evidence in humans for the nephrotoxicity of melamine, which previously had been described only in animals. The consequences of this outbreak are already severe and will likely continue to worsen. Herein we summarize the global impact of the melamine milk contamination, the reemergence of melamine-tainted animal feed, and potential mechanisms of melamine nephrotoxicity. Large-scale epidemiologic studies are necessary to further characterize this disease and to assess its potential long-term sequelae. This epidemic of environmental kidney disease highlights the morbidity associated with adulterated food products available in today's global marketplace and reminds us of the unique vulnerability of the kidney to environmental insults. Melamine is the latest in a growing list of diverse potentially toxic compounds about which nephrologists and other health-care providers responsible for the diagnosis and management of kidney disease must now be aware.
View details for DOI 10.1038/ki.2009.16
View details for Web of Science ID 000264747900005
View details for PubMedID 19212415
Mechanisms of ENaC regulation and clinical implications
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2008; 19 (10): 1845-1854
The epithelial Na+ channel (ENaC) transports Na+ across tight epithelia, including the distal nephron. Different paradigms of ENaC regulation include extrinsic and intrinsic factors that affect the expression, single-channel properties, and intracellular trafficking of the channel. In particular, recent discoveries highlight new findings regarding proteolytic processing, ubiquitination, and recycling of the channel. Understanding the regulation of this channel is critical to the understanding of various clinical phenomena, including normal physiology and several diseases of kidney and lung epithelia, such as blood pressure (BP) control, edema, and airway fluid clearance. Significant progress has been achieved in this active field of research. Although ENaC is classically thought to be a mediator of BP and volume status through Na+ reabsorption in the distal nephron, several studies in animal models highlight important roles for ENaC in lung pathophysiology, including in cystic fibrosis. The purpose of this review is to highlight the various modes and mechanisms of ENaC regulation, with a focus on more recent studies and their clinical implications.
View details for DOI 10.1681/ASN.2008020225
View details for Web of Science ID 000259830900005
View details for PubMedID 18753254
NH2 terminus of serum and glucocorticoid-regulated kinase 1 binds to phosphoinositides and is essential for isoform-specific physiological functions
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
2007; 292 (6): F1741-F1750
Serum and glucocorticoid regulated kinase 1 (SGK1) has been identified as a key regulatory protein that controls a diverse set of cellular processes including sodium (Na(+)) homeostasis, osmoregulation, cell survival, and cell proliferation. Two other SGK isoforms, SGK2 and SGK3, have been identified, which differ most markedly from SGK1 in their NH(2)-terminal domains. We found that SGK1 and SGK3 are potent stimulators of epithelial Na(+) channel (ENaC)-dependent Na(+) transport, while SGK2, which has a short NH(2) terminus, is a weak stimulator of ENaC. Further characterization of the role of the SGK1 NH(2) terminus revealed that its deletion does not affect in vitro kinase activity but profoundly limits the ability of SGK1 either to stimulate ENaC-dependent Na(+) transport or inhibit Forkhead-dependent gene transcription. The NH(2) terminus of SGK1, which shares sequence homology with the phosphoinositide 3-phosphate [PI(3)P] binding domain of SGK3, binds phosphoinositides in protein lipid overlay assays, interacting specifically with PI(3)P, PI(4)P, and PI(5)P, but not with PI(3,4,5)P(3). Moreover, a point mutation that reduces phosphoinositide binding to the NH(2) terminus also reduces SGK1 effects on Na(+) transport and Forkhead activity. These data suggest that the NH(2) terminus, although not required for PI 3-kinase-dependent modulation of SGK1 catalytic activity, is required for multiple SGK1 functions, including stimulation of ENaC and inhibition of the proapoptotic Forkhead transcription factor. Together, these observations support the idea that the NH(2)-terminal domain acts downstream of PI 3-kinase-dependent activation to target the kinase to specific cellular compartments and/or substrates, possibly through its interactions with a subset of phosphoinositides.
View details for DOI 10.1152/ajprenal.00027.2007
View details for Web of Science ID 000247942000010
View details for PubMedID 17356130
Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
2006; 291 (4): F714-F721
Regulation of ENaC occurs at several levels. The principal hormonal regulator of ENaC, aldosterone, acts through the mineralocorticoid receptor to modulate ENaC-mediated sodium transport, and considerable attention has focused on defining the components of the early phase of this response. Two genes, SGK1 and GILZ, have now been implicated in this regulation. While the functional significance of SGK1 in mediating aldosterone effects is well established, new evidence has enhanced our understanding of the mechanisms of SGK1 action. In addition, recent work demonstrates a novel role for GILZ in the stimulation of ENaC-mediated sodium transport. Interestingly, both SGK1 and GILZ appear to negatively regulate tonic inhibition of ENaC and thus use disinhibition to propagate the rapid effects of aldosterone to increase sodium reabsorption in tight epithelia.
View details for DOI 10.1152/ajprenal.00061.2006
View details for Web of Science ID 000240313000002
View details for PubMedID 16720863
AMP-activated kinase inhibits the epithelial Na+ channel through functional regulation of the ubiquitin ligase Nedd4-2
JOURNAL OF BIOLOGICAL CHEMISTRY
2006; 281 (36): 26159-26169
We recently found that the metabolic sensor AMP-activated kinase (AMPK) inhibits the epithelial Na+ channel (ENaC) through decreased plasma membrane ENaC expression, an effect requiring the presence of a binding motif in the cytoplasmic tail of the beta-ENaC subunit for the ubiquitin ligase Nedd4-2. To further examine the role of Nedd4-2 in the regulation of ENaC by AMPK, we studied the effects of AMPK activation on ENaC currents in Xenopus oocytes co-expressing ENaC and wild-type (WT) or mutant forms of Nedd4-2. ENaC inhibition by AMPK was preserved in oocytes expressing WT Nedd4-2 but blocked in oocytes expressing either a dominant-negative (DN) or constitutively active (CA) Nedd4-2 mutant, suggesting that AMPK-dependent modulation of Nedd4-2 function is involved. Similar experiments utilizing WT or mutant forms of the serum- and glucocorticoid-regulated kinase (SGK1), modulators of protein kinase A (PKA), or extracellular-regulated kinase (ERK) did not affect ENaC inhibition by AMPK, suggesting that these pathways known to modulate the Nedd4-2-ENaC interaction are not responsible. AMPK-dependent phosphorylation of Nedd4-2 expressed in HEK-293 cells occurred both in vitro and in vivo, suggesting a potential mechanism for modulation of Nedd4-2 and thus cellular ENaC activity. Moreover, cellular AMPK activation significantly enhanced the interaction of the beta-ENaC subunit with Nedd4-2, as measured by co-immunoprecipitation assays in HEK-293 cells. In summary, these results suggest a novel mechanism for ENaC regulation in which AMPK promotes ENaC-Nedd4-2 interaction, thereby inhibiting ENaC by increasing Nedd4-2-dependent ENaC retrieval from the plasma membrane. AMPK-dependent ENaC inhibition may limit cellular Na+ loading under conditions of metabolic stress when AMPK becomes activated.
View details for DOI 10.1074/jbc.M606045200
View details for Web of Science ID 000240249500032
View details for PubMedID 16844684
Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4-2 by inducing interaction with 14-3-3
2005; 19 (12): 3073-3084
Serum- and glucocorticoid-regulated kinase 1 (SGK1) is an aldosterone-regulated early response gene product that regulates the activity of several ion transport proteins, most notably that of the epithelial sodium channel (ENaC). Recent evidence has established that SGK1 phosphorylates and inhibits Nedd4-2 (neural precursor cell-expressed, developmentally down-regulated protein 4-2), a ubiquitin ligase that decreases cell surface expression of the channel and possibly stimulates its degradation. The mechanistic basis for this SGK1-induced Nedd4-2 inhibition is currently unknown. In this study we show that SGK1-mediated phosphorylation of Nedd4-2 induces its interaction with members of the 14-3-3 family of regulatory proteins. Through functional characterization of Nedd4-2-mutant proteins, we demonstrate that this interaction is required for SGK1-mediated inhibition of Nedd4-2. The concerted action of SGK1 and 14-3-3 appears to disrupt Nedd4-2-mediated ubiquitination of ENaC, thus providing a mechanism by which SGK1 modulates the ENaC-mediated Na(+) current. Finally, the expression pattern of 14-3-3 is also consistent with a functional role in distal nephron Na(+) transport. These results demonstrate a novel, physiologically significant role for 14-3-3 proteins in modulating ubiquitin ligase-dependent pathways in the control of epithelial ion transport.
View details for DOI 10.1210/me.2005-0193
View details for Web of Science ID 000233460500015
View details for PubMedID 16099816
SGK1: A rapid aldosterone-induced regulator of renal sodium reabsorption
2005; 20: 134-139
Recently, substantial progress has been made in understanding the mechanisms by which aldosterone rapidly stimulates sodium transport in the distal nephron and other tight epithelia. Serum- and glucocorticoid-regulated kinase 1 (SGK1) has been identified as an important mediator of this process. Its physiological relevance has been revealed through heterologous expression in cultured cells and generation of SGK1 knockout mice.
View details for DOI 10.1152/physiol.00053.2004
View details for Web of Science ID 000227958500008
View details for PubMedID 15772302
Recurrent and de novo diabetic nephropathy in renal allografts
2003; 75 (1): 66-71
Histologic findings of diabetic nephropathy (DN) are observed in allografts of patients with pretransplant (PreTx) diabetes mellitus (DM) and in patients who develop DM posttransplant (PostTx). Patients with allograft biopsies (Bx) were retrospectively studied to determine the incidence of recurrent and de novo DN and to ascertain what, if any, risk factors predispose to histologic DN in either patient population.From the renal transplant services at four hospitals from 1992 to 2000, the authors identified all patients with PreTxDM and PostTxDM (n=81). Those with renal biopsies performed >/=18 months PostTx were classified according to the presence or absence of histologic DN (Bx-positive, n=23; Bx-negative, n=35). Patients were then subdivided into four categories-recurrent DN (n=16), de novo DN (n=7), no recurrent DN (n=27), and no de novo DN (n=8)-for analyses.Among these 58 patients, 74.1% had PreTx and 25.9% had PostTx diabetes. Of those with histologic DN, 69.6% were recurrent DN and 30.4% were de novo DN, making de novo DN at least as likely to develop as recurrent DN. After the onset of diabetes in the de novo population, the time to development of histologic DN was similar in the recurrent and the de novo patients (6.68+/-3.86 years vs. 5.90+/-3.13 years, P=0.66) and more rapid than previously reported. Apart from a more frequent family history of hypertension in patients with allograft DN compared with those without allograft DN, known risk factors for the development of native DN did not significantly differ among patients in the four cohorts. Proposed risk factors related to transplantation did not correlate with the development of recurrent or de novo DN.Among patients with histologic DN, de novo DN occurred at least as frequently as recurrent DN, and the time to onset of histologically apparent DN was more rapid than previously reported. Neither the usual clinical predictors of DN nor clinical variables related to transplantation clearly distinguished the group with DN from the group without it, potentially implicating novel mechanisms in its pathogenesis.
View details for DOI 10.1097/01.TP.0000040870.94999.87
View details for Web of Science ID 000180617800012
View details for PubMedID 12544873