Late onset lupus nephritis: analysis of clinical manifestations and renal pathological features in Siriraj Hospital.

BACKGROUND: Lupus nephritis (LN) is uncommon after the age of 50 years and studies of elderly patients with LN are rare. The authors conducted the current study to determine the clinical manifestations, pathological features and prognosis of 30 Thai patients with late onset LN in Siriraj hospital in Bangkok from 1989 to 2006. MATERIAL AND METHOD: Thirty LN patients with a disease onset beyond the age of 50 years from 1989 to 2006 were enrolled in this retrospective study. All of them received renal biopsy. The histological classifications were categorized according to 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. RESULTS: Clinical and pathologic records were collected from 30 patients (23 female and 7 men) who were followed-up for a mean period of 25.8 months (range, 6 to 96 months). The mean age was 56.6 +/- 4 years. Hypertension was diagnosed in 66.7% of patients and 41.3% had serum creatinine greater than 1.5 mg/dL. Nephrotic-range proteinuria was found in 63.3% of patients and creatinine clearance less than 50 ml/min was found in 70%. Of the 30 patients, the most common renal histologic finding was diffuse proliferative glomerulonephritis (63.30%). The overall probability of patient survival was 94.1% at 12 months, 68.6% at 36 months and 34.3% at 60 months. During the follow-up period (25.8 months; range, 6 to 96 months), 4 patients died. Infection was the leading cause of death (75%). CONCLUSION: Lupus nephritis in the elderly patients is not uncommon. Prompt diagnosis should be made for appropriate management and optimal outcome.

Nephrotic syndrome in elderly patients: three years experience at Siriraj Hospital.

BACKGROUND: The population age is being high and nephotic syndrome is a common renal disease. OBJECTIVE: To find the etiology and clinical manifestations of nephrotic syndrome in the elderly patients who underwent renal biopsy at Siriraj hospital including management and outcome. MATERIAL AND METHOD: Retrospective study in 76 nephrotic patients whose age > or =50 years and underwent renal biopsy between 2005-2007. RESULTS: Seventy six nephrotic patients with age ranged from 50-84 years were analysed. Primary glomerulonephritis diseases were found more than secondary causes (5:2). The two most common glomerulonephritis were membranous GN and focal/segmental glomerulosclerosis. The etiology of common secondary GN was lupus nephtitis 11.84% following by diabetic nephropathy and amyloidosis. The patients received immunosuppressive drugs and complete response was found in 51%, partial response 10.2%, no response was 2% and no immunosuppressive therapy 36.7%. There was 1 patient died of septicaemia. CONCLUSION: Nephrotic syndrome in the elderly patients were not uncommon. The causes should be identified for prompt management and excellent outcome.

Clinical features and outcomes in patient with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment in Siriraj Hospital.

BACKGROUND: ANCA is detected in several vasculitic diseases, including drug-induced systemic vasculitis: propylthiouracil (PTU), hydralazine, minocycline, penicillamine, allopurinol, procainamide, carbimazole, thiamazole, clozapine and phenytoin. All have been known to induce ANCA positive vasculitis in adult patients. OBJECTIVE: To study the clinical manifestation, renal pathology and outcome of patients with ANCA positive vasculitis associated with propylthiouracil treatment in Siriraj Hospital. MATERIAL AND METHOD: Retrospective study in 7patients with Graves' disease who were treated with propylthiouracil and developed ANCA-positive glomerulonephritis between 2000-2008. RESULTS: Seven cases with Graves' disease who received propylthiouracil whose ages were 43 +/- 14 years. The duration of propylthiouracil treatment was 68.5 +/- 39 months and the doses were 50-150 mg per day. Six cases had P-ANCA and one case had C-ANCA in the serum. Proteinuria ranged from 0.49-2.9 gram per day. Mean serum creatinine was 2.05 mg/dl with creatinine clearance of 44 +/- 35 ml/min. The propylthiouracil was withdrawn in every patient and corticosteroid was administered. Renal remission was found until 1 year of follow-up. CONCLUSION: ANCA positive glomerulonephritis associated with propylthiouracil is not uncommon. The average onset of glomerulonephritis is 2 years or more. The propylthiouracil dosage was not necessary high. Urinalysis and other glomerulonephritis symptoms should be screened for early diagnosis and appropriate treatment in patients treated with PTU.

Non-diabetic glomerular disease in type II DM: 10 years experience.

BACKGROUND: The nature of renal damage in patients with type II diabetes remains unclear. OBJECTIVE: To analyze the renal histopathology in type II diabetes who underwent renal biopsy at Siriraj Hospital, renal unit over 10 year period. MATERIAL AND METHOD: The clinical and biochemical data in 54 patients with Type II DM, atypical cases of DN, were subjected to renal biopsy and analyzed retrospectively. RESULTS: Ten out of fifty-four type II diabetic patients (18.5%) were diagnosed non-diabetic nephropathy (NDN); there were 4 patients with membranous GN, 3 patients with crescentic GN1 patient of MPGN type I, 1 patient with renal change from hypertension and 1 patient with IgMN. The most important factor that had statistically significant was nephritis urine sediment (NDN: DN 40% vs. 4.5%), However 60% of NDN had no nephritic urine sediment. CONCLUSION: There was no strong predictor to differentiate DN from NDN by clinical or biochemical data. The only significant finding in NDN was nephritic urine sediment.

Arterial occlusion in nephrotic syndrome: report of four cases in Siriraj Hospital.

Venous thrombosis is commonly found in nephrotic syndrome, but arterial occlusion is never report in Thailand. Four cases with cerebral and femoral arteries occlusion were demonstrated. The early diagnosis and appropriate intervention can improve outcomes, reduce mortality and morbidity significantly.

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor.

Previous research on proteins that inhibit kidney stone formation has identified a relatively small number of well-characterized inhibitors. Identification of additional stone inhibitors would increase understanding of the pathogenesis and pathophysiology of nephrolithiasis. We have combined conventional biochemical methods with recent advances in mass spectrometry (MS) to identify a novel calcium oxalate (CaOx) crystal growth inhibitor in normal human urine. Anionic proteins were isolated by DEAE adsorption and separated by HiLoad 16/60 Superdex 75 gel filtration. A fraction with potent inhibitory activity against CaOx crystal growth was isolated and purified by anion exchange chromatography. The protein in 2 subfractions that retained inhibitory activity was identified by matrix-assisted laser desorption/ionization-time-of-flight MS and electrospray ionization-quadrupole-time-of-flight tandem MS as human trefoil factor 1 (TFF1). Western blot analysis confirmed the mass spectrometric protein identification. Functional studies of urinary TFF1 demonstrated that its inhibitory potency was similar to that of nephrocalcin. The inhibitory activity of urinary TFF1 was dose dependent and was inhibited by TFF1 antisera. Anti-C-terminal antibody was particularly effective, consistent with our proposed model in which the 4 C-terminal glutamic residues of TFF1 interact with calcium ions to prevent CaOx crystal growth. Concentrations and relative amounts of TFF1 in the urine of patients with idiopathic CaOx kidney stone were significantly less (2.5-fold for the concentrations and 5- to 22-fold for the relative amounts) than those found in controls. These data indicate that TFF1 is a novel potent CaOx crystal growth inhibitor with a potential pathophysiological role in nephrolithiasis.

A histopathological study of hearts and spleens of hamsters (Mesocricetus auratus) infected with Leptospira interrogans, serovar pyrogenes.

The effects of Leptospira interrogans on the heart and spleen of hamsters were studied histopathologically. Infected hamsters were sacrificed at 1 hour, 6 hours and on days 1, 2, 3, 4, 5 and 6 after inoculation with Leptospira interrogans serovar pyrogenes. The heart and spleen of each of the sacrificed animals were removed and processed for routine conventional light microscopy. Infected hearts showed degenerative change of the cardiac muscle cells composed of cellular swelling, condensation of chromatin granules, pyknotic nuclei and acidophilic cytoplasm. Congestion of the cardiac blood vessels and hemorrhagic areas were found. Necrosis of the cardiac muscle cells was surrounded by numerous inflammatory cells. In the spleen, cellular necrosis was found scattered throughout the splenic cord. The splenic sinusoids were dilated and congested with many hemorrhagic areas. Inflammatory cell infiltration was also noted in the splenic parenchyma and the splenic sinusoids.

The effect of alpha-tocopherol on the oxidative stress and antioxidants in idiopathic IgA nephropathy.

OBJECTIVE: Nearly 25% of IgA nephropathy patients progress to end-stage renal disease over a 20-25 year follow-up period. IgA containing immune complex stimulates oxygen free radical production by mesangial cells in vitro, which may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal damage in patients with IgA nephropathy. MATERIAL AND METHOD: Twenty-eight patients with idiopathic IgA nephropathy were supplemented with vitamin E 400 mg/day for 6 months. Antioxidant enzymes, glutathione, plasma malondialdehyde (MDA), and renal function were studied after 3 and 6 months therapy. RESULT: The result of the study showed high plasma MDA and significant reduction after therapy (1.15 +/- 0.45 VS 0.86 +/- 0.30 microM, p < 0.0001). The RBC vitamin E was also elevated statistically significantly (5.07 +/- 2.42 VS 15.70 +/- 3.37 microM, p < 0.001). Glutathione peroxidase activities were decreased (38.52 +/- 15.53 VS 23.97 +/- 7.63 U/gHb, p < 0.001). Glutathione was also decreased (44.80 +/- 9.70 VS 32.45 +/- 6.74 mg/dl, p < 0.05) but there were no changes in red cell catalase and superoxide dismutase activities. Creatinine clearance, proteinuria, urine N-acetyl glucosaminidase and beta2-microglobulin also showed no improvement. CONCLUSION: Our data demonstrated the particular group of IgA nephropathy patients with low vitamin E level and high oxidative stress had significant reduction of oxidative stress after vitamin E therapy.

Immunohistochemical study for the diagnosis of Alport's syndrome.

BACKGROUND: Alport's syndrome (AS) is the most common cause of inherited glomerular disease in Thailand. The majority of cases show X-linked inheritance, which is caused by mutations in the gene coding for the alpha5 chain of type IV collagen in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). Such mutation usually leads to a reduction in protein amount, thus, immunohistochemical studies have been considered in diagnostic evaluation. OBJECTIVE: To study the expression of alpha[IV] collagen chains in the skin as an alternative approach to diagnose AS. MATERIAL AND METHOD: Eleven unrelated probands with proven AS, 7 relatives with abnormal urinalysis, 4 suspected individuals, and 8 normal controls were enrolled. A punch skin biopsy and immunofluorescence staining of the tissue specimens for alpha1, alpha3 and alpha5[IV] collagen chains was performed. RESULTS: The alpha5[IV] chain was absent in the EBM in all male AS patients while a discontinuing pattern was observed in all females except one. The findings are specific for AS with a sensitivity of 91%. Studies in relatives and suspected individuals also confirmed the advantage of this approach as demonstrated by the absence and discontinuation of alpha5[IV] staining in all males and females, respectively. We also analyzed their expressions in the kidney tissue and demonstrated abnormal alpha3 and alpha5[IV] staining in five of six samples. CONCLUSION: Immunohistochemical study of the skin should be used as a screening method in patients suspected of AS, as it is much less invasive. Moreover, it is a useful adjunct to conventional examination of biopsied renal tissue.

An analysis of 3,555 cases of renal biopsy in Thailand.

BACKGROUND: The knowledge of the epidemiology of biopsied renal diseases provides useful information in clinical practice. There are several epidemiologic population-based studies of biopsy-proven nephropathies with detailed clinicopathologic correlations that could be different according to the country analyzed. OBJECTIVE: To identify the prevalence of primary and secondary glomerular diseases and to study the trend of the pattern changes of the glomerulopathy in Thailand. MATERIAL AND METHOD: A retrospective study of percutaneous renal biopsies during a 23-year period of 1982 to 2005 was performed. A total of 3,555 consecutive native kidney biopsies in adult patients between 12 and 84 years of age were analyzed for the prevalence and changes in the 5-year interval over the two decades. RESULTS: From the clinical trial of 3,275 patients, the ratio between primary and secondary glomerular diseases was 2:1 (2154:1121). The most common primary glomerular disease (2154 patients) were IgM nephropathy (n = 986, 45.8%) followed by IgA nephropathy (n = 386, 17.9%); membranous nephropathy (n = 341, 15.8%); diffuse endocapillary proliferative glomerulonephritis (n = 114, 5.3%) and diffuse crescentic glomerulonephritis (n = 71, 3.3%). Lupus nephritis was the most prevalent cause of secondary glomerulonephritis in the present study (n = 992, 88.5%). Examination of the 5-year interval along the study period revealed a significant increase in the prevalence of IgA nephropathy and diabetic nephropathy. Prevalence of focal and segmental glomerulosclerosis rose by five times over the last two decades in contrast to IgM nephropathy, which prevalence is decreasing. CONCLUSION: There is high prevalence of IgM nephropathy, IgA nephropathy, and lupus nephritis in Thailand which is different from other countries. It could be due to various races and altered environments. The information obtained from these results is an important contribution for the understanding of the prevalence in renal diseases in Thailand. It can be used as the baseline data for making efficient research into the appropriate and beneficial way of management in the future.

Systemic lupus erythematosus in Thai children: clinicopathologic findings and outcome in 82 patients.

OBJECTIVES: To define the patterns of clinicopathologic findings and to identify the risk factors for renal failure and mortality of childhood-onset systemic lupus erythematosus (SLE) in Thailand. MATERIAL AND METHOD: The study is a retrospective analysis of clinical manifestations, laboratory data, and pathologic findings, treatment modalities, and outcome of 82 patients with biopsy-proven lupus nephritis (LN) with disease onset between I January 1987 and 31 December 1997. All children developed these first manifestations at the age 13 years or under RESULTS: Sixty-four (789%) patients were females and eighteen (22%) were males (ratio female/male = 3.5:1). The patients were followed for a mean period of 53.6 months (range 1 -141). The mean age at disease onset was 9.2 years (range 2-12.6). Class-IV LN, observed in 40 (48.8%) patients, was the most frequent histopathology on initial renal biopsy. Less frequent findings were class-II (30.5%), V (14.6%), I (3.7%) and III (2.4%) LN. Based on the renal histopathology and clinical presentations, patients were treated with corticosteroids alone or in combination with azathioprine or with intravenous cyclophosphamide (CYC). Methylprednisolone pulses were given in patients with clinically more severe disease. Follow-up biopsies, performed in 12 patients, showed no change in 4 patients, and were progressive in 8 patients. On final clinical evaluation, 20 patients died, 65% died from serious infections, 15% from cardiopulmonary complications, and 10% from end stage renal disease. As the whole group, survival rates were 89% and 74% at 12 and 60 months, respectively. The 5-year patient survival in class-II, class-IV and class- VLN patients were 83%, 67% and 64%, respectively. Within the group of class-IV LN, the 5-year survival in the patients treated with intravenous CYC was significantly better than those receiving prednisolone with or without azathioprine. Five-year kidney survival rates from the time of diagnosis to the endpoints of terminal renal failure were 94% for the whole group, and 100%, 96%, 91% in the class- V, class-II, and class-IV group, respectively. Initial presence of hypertension, hematuria, renal insufficiency were independent factors significantly associated with lower patient survival probabilities. There was no association of either patient and kidney survival with gender, age, cytopenia, and autoantibody level. CONCLUSIONS: Infectious complications were the most common cause of morbidity and mortality in our pediatric patients with SLE. The immunosuppressive agents used to treat SLE seemed to be a major contribution to the patient survival. With judicious use of corticosteroid, intravenous CYC in severe SLE showed superior efficacy over oral prednisolone with or without azathioprine.

Percutaneous renal biopsy in children.

The authors studied the percutaneous renal biopsies performed in the Department of Pediatrics, Siriraj Hospital from January 2000 to March 2001 in order to evaluate the safety and benefit of the procedure. Eighty-five patients (90 episodes) were included in the study, aged 7.8+/-3.7 year (range 16 months to 16 years), with a male to female ratio of 1.2:1. Nephrotic syndrome (42.3%) and systemic lupus erythematosus (23.5%) were the two most common indications for biopsy. The kidney was localized by ultrasound prior to the procedure in nearly all cases (97.7%). Premedication with Ketamine was adequate in most patients (91.1%). A modified 13 G Vim-Silverman needle was used to obtain 1-4 biopsy cores. The mean number of glomeruli obtained was 44.0+/-29.9, with failure to obtain renal tissue in 6 episodes (6.6%). Percutaneous biopsy was performed twice in one patient without success and the patient eventually underwent an open biopsy. The most common complication was hematuria (74.4%), of these, gross hematuria was found in 23.3 per cent. Blood transfusion was needed in 2 patients, one of them also needed embolization to control bleeding. Transient hypotension occurred in 1 patient. Transient hypertension occurred in 6 episodes (6.6%). Muscle twitching occurred in 2 episodes and was treated with diazepam intravenously. Hypertension and muscle twitching only occurred in those who received ketamine. The Clinical Benefit Score was 2 (information yielding a definite diagnosis and/or prognosis, alternatively allowing a change in, or support of, therapy) in 89.4 per cent. It was concluded that the present practice of renal biopsy is safe, with high clinical benefit score. It remains to be studied whether an ultrasound guidance biopsy with a newer biopsy device will lower the incidence of complications even further.

Effect of fish oil on oxidative stress, lipid profile and renal function in IgA nephropathy.

The omega-3 polyunsaturated fatty acids in fish oil have been shown to produce beneficial effects, such as a reduction in blood pressure, proteinuria, lipid levels and inflammation. Aggregated immunoglobulin A obtained from IgA nephropathy patients induced greater oxygen free radicals in polymorphonuclear leukocytes than other glomerulopathy. All of which may affect the course of IgA nephropathy. Twenty-three adult patients with biopsy proven IgA nephropathy, with proteinuria more than 1 g/day, serum creatinine less than 3 mg/dl and blood pressure control less than 130/80 mmHg were given omega-3 polyunsaturated fatty acids (PUFA) in the form of an Omacor capsule 4 g/day equivalent to eicosapentaenoic acid (EPA) 1.88 g and docosahexaenoic acid (DHA) 1.48 g for 6 months. A 3 to 6 month follow-up was planned, with monthly evaluations of the patients. By six months, the serum triglyceride was significantly reduced (143.45 +/- 62.65 vs 91 +/- 42.89 mg/dl, p = 0.002), serum cholesterol was also reduced but not statistically significant (234.16 +/- 56.29 vs 219.76 +/- 51.25 mg/dl, p = 0.07). There was a trend of increased serum high density lipoprotein (HDL)-cholesterol (39.26 +/- 10.56 vs 42.72 +/- 8.37 mg/dl, p = 0.056). Urine beta-2-microglobulin was elevated in IgA patients and decreased statistically significant after 3 months (453 +/- 580 vs 308 +/- 274 microg/24 h, p < 0.001) and 6 months of fish oil therapy (453 +/- 580 vs 142 +/- 182, p < 0.03) while urine N-acetyl-glucosaminidase (NAG) was of no significant difference both before and after fish oil administration (21 +/- 10 vs 22 +/- 10 and 21 +/- 9 U/24 h, p = 0.08). Plasma malondialdehyde (MDA), the end product of oxidative stress was statistically, significantly decreased (1.09 +/- 0.51 vs 0.89 +/- 0.49 nmol/L, p = 0.003). The study did not show any change in blood pressure, proteinuria, or serum creatinine. The authors conclude from the results of this study that patients with idiopathic IgA nephropathy with proteinuria and mildly reduced GFR did not benefit from short-term treatment with 4 g per day of omega-3 PUFA regarding the total protein excretion and glomerular filtration rate (GFR), but the advantage was the improvement in tubular dysfunction, lipid profiles, and oxidative stress.

Prevalence and clinicopathologic findings of antiphospholipid syndrome nephropathy in Thai systemic lupus erythematosus patients who underwent renal biopsies.

AIM: To determine the prevalence of antiphospholipid syndrome nephropathy (APSN) in Thai systemic lupus erythematosus (SLE) patients who underwent renal biopsy and to compare the relationship of renal histopathology and other significant clinical parameters between SLE patients with and without APSN. METHODS: A retrospective analysis was undertaken in systemic lupus erythematosus patients (n = 150, 44 <15 years old, 106 0e;15 years old) who underwent renal biopsy. The specimens were evaluated for histological features of APSN and other significant clinical parameters. The result of antiphospholipid antibodies, clinical course, and renal function from chart review were analysed. RESULTS: The prevalence of APSN in systemic lupus erythematosus patients who underwent renal biopsies was 34% (16% in <15-year-old group, 41.5% in > or =15-year-old group). APSN was associated with more severe hypertension (P = 0.002 for systolic and P = 0.004 for diastolic blood pressure), acute renal failure (P = 0.003), persistent heavy proteinuria (P < 0.001 for 4+ proteinuria), severe lupus nephritis (class III and IV, P = 0.014, high activity and chronicity indices, P < 0.001) and a tendency to progress to end-stage renal disease. CONCLUSION: Systemic lupus erythematosus patients who underwent renal biopsies in our institute showed a prevalence of APSN comparable to those in western countries. The presence of APSN was significantly higher in the adult than in the paediatric population. Its association with poor prognostic indicators suggests poor renal outcome. Clinicians should be aware of this condition in order to give proper care to systemic lupus erythematosus patients.

Proteomic identification of altered proteins in skeletal muscle during chronic potassium depletion: Implications for hypokalemic myopathy.

Prolonged potassium depletion is a well-known cause of myopathy. The pathophysiology of hypokalemic myopathy, however, remains unclear. We performed a gel-based, differential proteomics study to define altered proteins in skeletal muscles during chronic potassium depletion. BALB/c mice were fed with normal chow (0.36% K+) or K+-depleted (KD) diet (<0.001% K+) for 8 weeks (n = 5 in each group). Left gastrocnemius muscles were surgically removed from each animal. Histopathological examination showed mild-degree infiltration of polymornuclear and mononuclear cells at the interstitium of the KD muscles. Extracted proteins were resolved with two-dimensional electrophoresis (2-DE), and visualized with Coomassie Brilliant Blue R-250 stain. Quantitative intensity analysis revealed 16 up-regulated protein spots in the KD muscles, as compared to the controls. These differentially expressed proteins were subsequently identified by peptide mass fingerprinting and by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Most of the altered proteins induced by chronic potassium depletion were muscle enzymes that play significant roles in several various metabolic pathways. Other up-regulated proteins included myosin-binding protein H, alpha-B Crystallin, and translationally controlled tumor protein (TCTP). These findings may lead to a new roadmap for research on hypokalemic myopathy, to better understanding of the pathophysiology of this medical disease, and to biomarker discovery.

Proteomic identification of alterations in metabolic enzymes and signaling proteins in hypokalemic nephropathy.

Hypokalemic nephropathy caused by prolonged K(+) deficiency is associated with metabolic alkalosis, polydipsia, polyuria, growth retardation, hypertension, and progressive tubulointerstitial injury. Its pathophysiology, however, remains unclear. We performed gel-based, differential proteomics analysis of kidneys from BALB/c mice fed with high-normal-K(+) (HNK), low-normal-K(+) (LNK), or K(+)-depleted diet for 8 wk (n = 6 in each group). Plasma K(+) levels were 4.62 +/- 0.35, 4.46 +/- 0.23, and 1.51 +/- 0.21 mmol/L for HNK, LNK, and KD mice, respectively (p < 0.0001; KD vs. others). With comparable amounts of food intake, the KD mice drank significantly more water than the other two groups and had polyuria. Additionally, the KD mice had growth retardation, metabolic alkalosis, markedly enlarged kidneys, renal tubular dilation, intratubular deposition of amorphous and laminated hyaline materials, and tubular atrophy. A total of 33 renal proteins were differentially expressed between the KD mice and others, whereas only eight proteins were differentially expressed between the HNK and LNK groups, as determined by quantitative intensity analysis and ANOVA with Tukey's post hoc multiple comparisons. Using MALDI-MS and/or quadrupole-TOF MS/MS, 30 altered proteins induced by K(+)-depletion were identified as metabolic enzymes (e.g., carbonic anhydrase II, aldose reductase, glutathione S-transferase GT41A, etc.), signaling proteins (14-3-3 epsilon, 14-3-3 zeta, and cofilin 1), and cytoskeletal proteins (gamma-actin and tropomyosin). Some of these altered proteins, particularly metabolic enzymes and signaling proteins, have been demonstrated to be involved in metabolic alkalosis, polyuria, and renal tubular injury. Our findings may lead to a new road map for research on hypokalemic nephropathy and to better understanding of the pathophysiology of this medical disease when the functional and physiological significances of these altered proteins are defined.