Mesangial IgA Nephropathy Research Articles

Mild mesangial proliferative IgA nephropathy with and without minimal change disease.

Mild mesangial proliferative IgA nephropathy with minimal change disease (MCD-IgAN) and mild mesangial proliferative IgA nephropathy without minimal change disease (Non-MCD-IgAN) have similar characteristics on light microscopy. Nevertheless, their discrepancies in clinicopathological features and prognosis remain unknown. A total of 589 patients with biopsy-proven mild mesangial proliferative IgA nephropathy (M-IgAN) combined with light microscopy and immunofluorescence were enrolled. Firstly, the diagnoses of the patients by electron microscopy were recorded and used as the gold standard. We calculated the sensitivity and specificity using nephrotic syndrome (NS) as the diagnostic criteria to identify MCD-IgAN. Then, excluding patients with a 24-h urinary total protein less than 0.5g/day, incomplete clinical data, or less than the six-month follow-up, we included 184 cases of non-MCD-IgAN and 98 cases of MCD-IgAN. The patients' clinicopathological and outcome data were collected and compared. Among the 589 patients, according to electron microscopy, 381 were diagnosed with non-MCD-IgAN, 167 with MCD-IgAN, and 41 with M-IgAN complicated by other glomerular diseases. Using NS as the diagnostic criteria to distinguish non-MCD-IgAN and MCD-IgAN, the sensitivity and specificity were 83.8% and 99.5%, respectively. The patients in the MCD-IgAN group tended to be younger, hypotensive, with lower urinary erythrocytes, and more likely to achieve complete remission, and fewer patients progressed to the endpoint than those in the non-MCD-IgAN group (all P < 0 .05). NS appears to be an objective indicator for differentiating MCD-IgAN from non-MCD-IgAN. Non-MCD-IgAN varies greatly from MCD-IgAN in clinicopathology and treatment response, with a poorer prognosis.

Mesangial C3 Deposition, Complement-Associated Variant, and Disease Progression in IgA Nephropathy.

IgA nephropathy is the most common primary GN worldwide, with dominant deposition of IgA and co-deposits of complement component 3 (C3). Phenotypes and progression of IgA nephropathy varies among different ethnic populations, while patients with IgA nephropathy from Asia showed more severe clinical phenotypes, active kidney lesions, and rapid progression. Our previous genome-wide association study identified complement factor H ( CFH ) variant rs6677604, tightly linked with the deletion of CFH -related protein 3 and CFH -related protein 1 genes ( ΔCFHR3-1 ), as IgA nephropathy susceptible variant, and additionally revealed its effect on complement regulation in IgA nephropathy. To further explore the effect of rs6677604 on IgA nephropathy progression, here we enrolled a Chinese IgA nephropathy cohort of 1781 patients with regular follow-up for analysis. The rs6677604 genotype was measured, and the genotype-phenotype correlation was analyzed using the t test, the chi-squared test, or the nonparametric test, and the association between rs6677604 genotype or mesangial C3 deposition and IgA nephropathy prognosis was analyzed using Kaplan-Meier analysis and Cox regression. We found that patients with rs6677604-GG genotype had a stronger intensity of mesangial C3 deposition than those with the rs6677604-AA/AG genotype. Patients with IgA nephropathy who had stronger intensity of C3 deposition manifested with more severe clinical and pathological manifestations, including lower eGFR and higher Oxford-M/S/T/C (mesangial hypercellularity, endocapillary cellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and crescent) scores. In the survival analysis, stronger intensity of mesangial C3 deposition, but not rs6677604-GG genotypes, was associated with poor long-term kidney outcome in IgA nephropathy. We found that in Chinese patients with IgA nephropathy, variant rs6677604 was associated with mesangial C3 deposition, and mesangial C3 deposition, but not rs6677604, was associated with IgA nephropathy severity and progression.

Status of Hepatitis B Virus Surface Antigen (HBsAg) Deposition in Renal Tissue among Glomerulonephritis Patients

Background: Hepatitis B virus (HBV) related glomerulonephritis (GN) may be found in HBV seropositive as well as seronegative patients. HBV may present in the renal tissue of such patients. Objective: The purpose of the present study was to assess status of HBsAg deposition in renal tissue among glomerulonephritis patients. Methodology: This cross-sectional study was conducted in the Department of Nephrology at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh during the period of July 2015 to June 2016. All diagnosed GN patients both HBV seropositive and seronegative aged more than 18 years of both sexes admitted in the department of Nephrology BSMMU were taken as the study population. Serological tests both HBsAg and anti-HBc (total) were done to identify the HBV seropositive and seronegative individuals by ELISA technique and Chemiluminescense Method respectively. Renal biopsy was done percutaneously through a posterior approach. Immunohistochemistry and one core were preserved in normal saline for direct immunofluorescence (DIF). Both test tubes were sent to find out histological features and presence of HBsAg in renal biopsy tissue in Pathology Department of Bangabandhu Sheikh Mujib Medical University, Dhaka. Results: HBsAg antigen in renal tissue was found in 2 patients among 7 patients who were seropositive for both HBsAg and Anti-HBc antibody (total), 2 patients among 8 patients who were HBsAg seronegative but Anti-HBc (total) seropositive, 2 patients among 38 patients who were seronegative for both HBsAg and Anti-HBc (total). There were no patients in this study who was HBsAg seropositive but Anti HBc (total) seronegative. Total 11.3% (6 patients) of renal biopsy specimens were found to have HBsAg deposits which included 3 cases of Membranoproliferative GN and one of each of Membranous nephropathy, Mesangial proliferative GN and IgA nephropathy. Conclusion: The high rate of HBsAg deposits has been found in renal tissue among GN patients. Bangladesh Journal of Medical Microbiology, January 2022;16(1):14-18

Relationship of HBsAg and Kidney Biopsy Marker with HBV Related Glomerulonephropathy

Hepatitis B virus infection is a major public health problem worldwide and it causes not only hepatic diseases but also extra hepatic manifestations particularly HBV-associated Glomerulo- nephritis (GN). HBsAg has been observed in the glomeruli of some patients with glomerulonephritis. HBV related glomerulo- nephritis may be found in HBV seropositive as well as sero- negative patients. HBV may present in the renal tissue of such patients. In most cases detection of HBsAg in the renal tissue by renal biopsy and immunohistochemistry can establish the etiology. To find out the relationship of HBsAg and Kidney biopsy marker with HBV related glomerulonephropathy, this cross sectional study was done in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), during the period of July 2015 to June 2016. A total number of 53 cases who fulfilled the inclusion and exclusion criteria were selected as sample. Samples were selected by purposive sampling technique. HBsAg antigen in renal tissue was found in 2 patients among 7 patients who were seropositive for both HBsAg and Anti HBc(total), 2 patients among 8 patients who were HBsAg seronegative but Anti HBc (total) seropositive, 2 patients among 38 patients who were seronegative for both HBsAg and Anti HBc(total). There were no patients in this study who was HBsAg seropositive but Anti HBc (total) seronegative. Total 11.3% (6 patients) of renal biopsy specimens were found to have HBsAg deposits which included 3 cases of Membrano- proliferative GN and one of each of Membranous nephropathy, Mesangial proliferative GN and IgA nephropathy. The high rate of HBsAg deposits found in renal tissue indicates that detection of HBsAg deposition should be done for all histological varieties of GN. Antiviral therapy may be used to stop progression of HBV associated nephropathy.&#x0D; Bangladesh Med J. 2021 Sept; 50(3): 1-6

Renal manifestations in rheumatoid arthritis and spondylarthritis

As systemic diseases it is not uncommon for inflammatory rheumatic diseases to exhibit renal involvement. In contrast to connective tissue diseases and vasculitis, in rheumatoid arthritis and spondylarthritis direct inflammatory manifestations in the sense of glomerulonephritis (GN) and autoimmune interstitial nephritis are rare. In these groups of diseases renal biopsies usually show mesangial proliferative GN and IgA nephropathy or less commonly membranous GN. These and secondary amyloid A (AA) amyloidosis are regularly associated with longer lasting disease activity and a poor prognosis; however, clinically more frequent and more relevant are other sequelae of chronic systemic inflammation, namely endothelial function disorder and the premature development of atherosclerosis, resulting in progressive kidney failure. This is accompanied by the undesired effects of antirheumatic treatment and renal complications of comorbidities.

Epidemiology of biopsy-proven glomerular diseases in Chinese children: A scoping review.

Glomerular disease is the leading cause of chronic kidney disease globally. No scoping review reports have focused on China's spectrum of glomerular diseases in children. This study aimed to systematically identify and describe retrospective studies on pediatric glomerular disease based on available data on sex, age, study period, and region. Six databases were systematically searched for relevant studies from initiation to December 2021 in PubMed, Embase, Web of Science, Global Health Library, Wangfang Database, and CNKI. Thirty-four studies were identified in the scoping review, including 40,430 patients with biopsy-proven diagnoses. The proportion of boys was significantly higher than that of girls. In this study, 28,280 (70%) cases were primary glomerular disease, 10,547 (26.1%) cases were diagnosed as secondary glomerular disease, and 1146 (2.8%) cases were hereditary glomerular disease. Minimal change disease is the most common glomerular disease among children in China, followed by mesangial proliferative glomerulonephritis, IgA nephropathy, and purpura nephritis. We observed increments in glomerular diseases in periods 2 (2001-2010) and 3 (2011-2021). The proportion of major glomerular diseases varies significantly in the different regions of China. The spectrum of pediatric glomerular diseases varied across sex, age groups, study periods, and regions, and has changed considerably over the past 30 years.

Case Report: Silicosis and IgA nephropathy, an exceptional association

A 57-year-old male who had been working in masonry for 33 years was hospitalized for renal function decline associated with exertional dyspnea. He presented with hypertension and limb edema. Urinalysis revealed an active urine sediment with glomerular proteinuria at 1.5 g/24h and the renal biopsy identified mesangial IgA Nephropathy. Chest tomography scans showed signs of silicosis. The patient received Angiotensin-Converting Enzyme Inhibitors with stable renal function. To our knowledge, the association of silicosis-IgA nephropathy has rarely been reported in the literature. This case highlights the effect of chronic exposure to silica dust and its association with both silica and renal disease.

Case Report: Silicosis and IgA nephropathy, an exceptional association

A 57-year-old male who had been working in masonry for 33 years was hospitalized for renal function decline associated with exertional dyspnea. He presented with hypertension and limb edema. Urinalysis revealed an active urine sediment with glomerular proteinuria at 1.5 g/24h and the renal biopsy identified mesangial IgA Nephropathy. Chest tomography scans showed signs of silicosis. The patient received Angiotensin-Converting Enzyme Inhibitors with stable renal function. To our knowledge, the association of silicosis-IgA nephropathy has rarely been reported in the literature. This case highlights the effect of chronic exposure to silica dust and its association with both silica and renal disease.

SAT-119 Gynecomastia and chronic renal failure: about 2 cases

Gynecomastia is a hyperplasia of the mammary glandular tissue. This is a common symptom in nephrology, responding to many etiologies. We report the observations of 2 renal failure patients with gynecomastia. Case 1: A 42-year-old man followed for chronic renal failure secondary to mesangial IgA nephropathy. The end stage was retained and the patient chose hemodialysis. He consulted for bilateral gynecomastia. Biological investigations showed normal gonadotropin levels and hyperprolactinemia at 4285 m U / L. Magnetic resonance imaging showed the absence of microadenoma and the presence of an arachnoidocele, which could explain hyperprolactinemia by disconnection. The patient was put under Bromocriptine and the evolution was marked by the decrease of the prolactinemia to 481 m U / L in 4 months. Case 2: A 56-year-old man, hypertensive, diabetic at the stage of degenerative complications. He is in chronic renal failure requiring 3 sessions per week of hemodialysis. He consulted for a firm and bilateral retro-areolar swelling. A mammary ultrasound concluded the presence of bilateral nodular gynecomastia without suspicious tissue injury. An iatrogenic cause was eliminated by the interrogation. The prolactin level was normal (436 m U / L). The mechanism of appearance of gynecomastia in chronic hemodialysis remains unclear. It has often been linked to a food or iatrogenic cause. Gynecomastia is often responsible for the alteration of sexual functions in men.

Abnormal IgA1 O-Glycosylation in a Multi-ethnic population of IgA Nephropathy Patients in KwaZulu Natal, South Africa.

Abnormal IgA1 O-Glycosylation in a Multi-ethnic population of IgA Nephropathy Patients in KwaZulu Natal, South Africa.

Clinical Implication of Latant Mesangial IgA Deposition in Renal Allograft Donors in Korea

Objectives: Mesangial IgA deposition is incidentally detected in asymptomatic populations. This study was to investigate the incidence and the latent mesangial IgA deposit in the donor kidney and its course after kidney transplantation. The effects of mesangial IgA deposit on clinical outcome was also evaluated. Methods: Retrospective chart review was conducted of who underwent kidney transplantation with zero time biopsies between January 2008 and December 2010 at Seoul National University Hospital. Incidence, short-term clinical outcome, and presence of mesangial IgA deposition in serial protocol biopsy were assessed. Mesangial IgA deposition was analysed by Electron microscope and immunofluorescent staining. Results: Mesangial IgA deposition and IgA nephropathy were present in 30(9.3%)and 17(5.3%) of the total 321 zero-time allograft biopsies. The 23 of 30 patients were performed serial protocol biopsy. Mesangial IgA deposition of 14 patients were disappeared on the 10th day protocol biopsy. The Mesangial IgA deposition was disappeared within six months in four patients, and one year after in three patients. One patient biopsy was proved IgA nephropathy in 10th day protocol biopsy. another two patients were loss of follow up biopsy after 10th day protocol biopsy. There was no association between clinicopathologic finding and early disappearance of mesangial IgA deposition. Renal function was fair during follow up period. Conclusion: The incidence of mesangial IgA deposit and IgA nephropathy is 14.6% in donor populations. Mesangial IgA depositions in zero-time biopsies were disappeared within one year in majority of the cases, and graft function was maintained while short-term follow-up period. However, more prospective researches are needed.

A case of membranous nephropathy associated with relapsing polychondritis

Relapsing polychondritis (RP) is a rare, chronic, and potentially fatal multisystemic inflammatory disorder targeting cartilaginous structures. This disorder is frequently associated with rheumatoid arthritis, systemic vasculitis, connective tissue diseases, and hematologic disorders, but renal involvement is unusual. In the literature, associated renal pathology includes mesangial expansion, IgA nephropathy, tubulointerstitial nephritis, and segmental necrotizing crescentic glomerulonephritis. We report a case of a 49-year-old male found to have RP and nephrotic syndrome, with confirmed membranous nephropathy on kidney biopsy. He responded well to corticosteroids and cyclosporine. This is the first case of renal associated RP confirmed by renal biopsy in Korea. Membranous nephropathy associated with RP has never before been reported.

CD248+ stromal cells are associated with progressive chronic kidney disease

Stromal fibroblasts are the primary cells of the kidney that produce fibrotic matrix. CD248 is a stromal marker expressed on fibroblasts and pericytes within the human kidney. Here, we tested whether CD248 expression in the kidney colocalizes with fibrosis and if it is associated with known determinants of chronic kidney disease (CKD). CD248 expression was located and quantified in situ by immunohistochemistry in kidney biopsies from 93 patients with IgA nephropathy and compared with 22 archived biopsies encompassing normal kidney tissue as control. In normal kidney tissue, CD248 was expressed by resident pericytes, stromal fibroblasts, and was upregulated in human CKD. The expression was linked to known determinants of renal progression. This relationship was maintained in a multivariate analysis with CD248 expression linked to renal survival. CD248 was expressed by a population of α-smooth muscle actin (SMA)(+) myofibroblasts and α-SMA(-) stromal cells but not expressed on CD45(+) leukocytes. Thus, CD248 defines a subset of stromal cells, including but not limited to some myofibroblasts, linked to albuminuria and tubulointerstitial damage during tissue remodeling in CKD.

Transactivation of RON receptor tyrosine kinase by interaction with PDGF receptor β during steady-state growth of human mesangial cells

Although it is well known that platelet-derived growth factor (PDGF) causes mesangial cell proliferation (presumably contributing to progression of glomerular disease), targeted inhibition of the PDGF receptor system has shown only limited efficacy against glomerular diseases. To examine whether this discrepancy is due to the involvement of other pathways, we used phosphorylated receptor tyrosine kinase arrays and found that RON (recepteur d'origine nantais) was phosphorylated while the PDGF receptor was dephosphorylated (thus inactive) in human mesangial cells (HMCs) at the time of cell cycle entry. Further, RON remained active during steady-state growth. Activation of RON was independent of its canonical ligand, macrophage-stimulating protein, but was mediated by transactivation from the PDGF-engaged PDGF receptor. Following stimulation with PDGF we found that the two receptors physically interacted. Knockdown of RON by siRNA increased the number of apoptotic cells without affecting the rate of DNA synthesis, suggesting that RON has anti-apoptotic functions. Immunohistochemical analysis found phosphorylated RON in glomerular lesions of patients with IgA nephropathy but not those with minimal change nephrotic syndrome, a disease not associated with mesangial proliferation. These results suggest that RON is involved in mesangial cell proliferation under both physiological and pathological conditions, and may be a relevant target for therapeutic intervention.

Megalin contributes to the early injury of proximal tubule cells during nonselective proteinuria

Megalin, a member of the LDL receptor family, is expressed on the apical membrane of proximal tubules and serves as an endocytic scavenger of filtered proteins and hence might contribute to the tubule injury as a consequence of glomerular disease. To study its role, we crossed megalin knockout mosaic mice (lacking megalin expression in 60% of proximal tubule cells) with NEP25 mice (a transgenic line expressing human CD25 in the podocyte). Treatment of this transgenic mouse with the immunotoxin causes nephrotic syndrome, focal segmental glomerulosclerosis and tubule-interstitial injury. Following this treatment, the double transgenic mice had massive non-selective proteinuria and mild glomerular and tubular injury. Comparison of megalin-containing to megalin-deficient proximal tubule cells within each kidney showed that albumin, immunoglobulin light chain, IgA and IgG were preferentially accumulated in proximal tubule cells expressing megalin. Tubule injury markers such as heme-oxygenase-1, monocyte chemoattractant protein-1 and cellular apoptosis were also preferentially found in these megalin-expressing cells. These results show that megalin plays a pivotal role in the reabsorption of small to large molecular size proteins and provides direct in vivo evidence that reabsorption of filtered proteins triggers events leading to tubule injury.

The metabolism of C9 in normal subjects and in patients with autoimmune disease.

The metabolism of the ninth component of complement (C9) was studied in eight healthy subjects and nine patients with autoimmune disease, including seven with systemic lupus erythematosus (SLE) and one each with mesangial IgA nephropathy and mixed essential cryoglobulinaemia. In normal subjects the metabolic parameters(mean +/- s.d.) were : fractional catabolic rate (FCR): 2.92 +/- 0.36%/h, plasma half-life (T1/2): 42.5 +/- 6.7 h, and extravascular/intravascular distribution ratio (EV/IV): 0.56 +/- 0.12. In patients the FCR was 3.38 +/- 0.70%/h, the T1/2 was 37.6 +/- 10.2 h, and the EV/IV was 0.55 +/- 0.19. Patients with reduced total serum haemolytic activity (i.e. CH50 <68% of normal human serum (NHS), N=7) had significantly higher FCR (3.57 +/- 0.67%/h) and shorter T1/2(33.5 +/- 6.8 h) than the control group (both P<0.05). The plasma concentration of the terminal complement complex (i.e. soluble TCC or SC5b-9) was higher in patients (median (range): 515 (300-1879 micrograms/l) than in normal subjects (313 (229-402 micrograms/liters): P<0.01) and showed a positive correlation with the FCR of C9 (r=0.61, P<0.01). Plasma C9 production rate was also greater in patients (0-11 +/- 0-05 mg/kg per h) compared with control subjects (0-07 +/- 0.03 mg/kg per h, P<0.05), and was associated with a higher C9 concentration in patients' sera (76 +/- 13 mg/l versus 61 +/- 14 mg/l, P<0.05). These results demonstrate that C9 is rapidly metabolized in normal humans and that hypercatabolism occurs in patients with autoimmune disease and complement activation. This was despite the presence of normal or elevated serum C9 levels and normal compartmental distribution.

Complications of IgA nephropathy in a non-insulin-dependent diabetes model, the Akita mouse.

The Akita mouse, which has a mutation (Cys96Tyr) in the insulin 2 gene (Ins2(Akita)), is a model for diabetes. The male Akita mouse has diabetes, while females develop mild diabetes. This study aimed to investigate renal complications in the Akita mouse model, which has been maintained in a heterozygous state Ins2(Akita) (+/-) with a C57BL/6 background (B6). Renal function (BUN, creatinine), serum IgA concentrations and histological changes in the kidneys were evaluated in diabetic and control mice in a B6 background. Five each of male and female mice per group (diabetes vs. control) were killed at 10, 20, 30 and 40 weeks of age. The influence of major histocompatibility antigens (MHC) on renal complications was tested using male diabetic mice in a C3H/He (C3H) background. When compared with controls, diabetic males, but not females, developed impaired renal function with elevation of serum IgA after 30 weeks of age. Diabetic glomerulosclerosis advanced with age in both sexes. Diffuse granular mesangial deposits of IgA were detected by immunofluorescence microscopy in diabetic males after 20 weeks. We tested whether the IgA-associated lesions were influenced by MHC using diabetic males in a C3H background. Similar degrees of diabetic glomerulosclerosis and glomerular IgA deposition were found in mice with C3H and B6 backgrounds. Akita mouse is a unique mouse model showing both mesangial sclerosis and IgA nephropathy.

Corticosteroid treatment of diffuse mesangial proliferative IgA nephropathy

Corticosteroid treatment of diffuse mesangial proliferative IgA nephropathy

Expression of mesangial IgA nephropathy in a family with several HLA‐dentical members

SUMMARY: The familial incidence of mesangial IgA nephropathy (IgAN) is well recognized. However, the genetic implications of this finding remain uncertain. We report a family of East Timorese origin where six out of eight members, including the mother and five first‐degree offspring, have had histologically proven mesangial IgAN. All eight members have undergone HLA A, B, C and DR typing as well as determination of C4 allotype. Among the offspring, there are HLA‐identical male twins (A11,‐; B13,15; Cw3,‐; DR2,3) and three HLA‐identical females (A11,‐; B13,27; Cw3,‐; DR2,3). Their C4 allotype is also identical (i.e. A3; B1,2,96 and A3; B1,96, respectively). There were histological and biochemical differences between the twins: subject ii‐2 showed focal mesangial proliferation on light microscopy and a 24 h urine protein excretion of 1–2 g on presentation while subject ii‐3 was normal at that time. the latter subsequently underwent a renal biopsy 15 years later and this showed changes only on immunofluorescence microscopy. There were major differences in expression of renal disease among the HLA‐identical sisters: two developed end‐stage renal failure (ESRF) by the age of 30 years, while the third retains normal renal function after 15 years follow‐up. the angiotensin converting enzyme (ACE) genotype was examined for insertion (I)/deletion (D) polymorphism; this showed that both patients with severe renal disease had the ID genotype and this was also present in the two unaffected female members. the study shows no relationship between the HLA A, B, C, DR, C4 supratype and progress of renal disease in this family with mesangial IgAN. Moreover, no association could be demonstrated between progress and the ACE genotype, although the number of patients involved was small. the data suggest that environmental factors and/or genetic/environmental interaction influence the severity of renal injury.

End-stage renal disease in China

A 33-year-old man with chronic renal failure due to glomerulonephritis was referred to the Jinling Hospital because of severe anemia, anorexia, nausea, and weakness during the preceding 2 months. Ten years ago, he was diagnosed as having chronic nephritis with proteinuria, hematuria, and edema. Renal biopsy performed 8 years ago revealed mesangial IgA nephropathy with marked glomerulosclerosis. He received corticosteroids and dipyridamole for 8 months without apparent effect. For the past 7 years, he had been told that his serum creatinine and BUN levels were increased above normal and that his blood pressure had reached 170/120 mm Hg. He was advised by his doctor to eat a low-protein and low-salt diet and was prescribed antihypertensive and diuretic medications. Proteinuria persisted, the anemia and hypertension worsened, and he experienced frequent attacks of dizziness accompanied by nausea and vomiting. Physical examination revealed a slender, undernourished man; his height was 175 cm and weight 53 kg. His blood pressure was 180/110 mm Hg. Funduscopic examination showed narrowing of retinal arterioles. Cardiac examination disclosed a precordial thrust and a grade Il/Ill apical systolic murmur. He had mild pedal edema; the physical examination otherwise was unremarkable. Serum biochemistry values were: blood urea nitrogen, 65 mg/dl; serum creatinine, 6.4 mg/dl; creatinine clearance, 13 mI/mm; sodium, 142 mEq/ liter; potassium, 3.8 mEq/liter; chloride, 110 mEq/liter; calcium, 8.0 mg/dl; phosphorus, 4.6 mg/dl; bicarbonate, 24 mEq/liter; uric acid, 11.9 mg/dl; alkaline phosphatase, 68 U/liter; triglycerides, 99 mg/dl; and cholesterol, 192 mg/dl. His hematocrit was 25%, and the white blood cell count and platelet count were normal. The blood pH was 7.33. Urinalysis revealed the following: pH, 5.2; protein, 2.82 g/24 hr; red blood cell count, 0-2/high-power field. Electrocardiogram showed mild left-ventricular hypertrophy with abnormal T-waves. A chest radiograph revealed no