Incidence of De Novo Post-Transplant Malignancies in Thai Adult Kidney Transplant Recipients: A Single-Center, Population-Controlled, Retrospective Cohort Study at the Highest Volume Kidney Transplant Center in Thailand.

Kidney transplant recipients (KTRs) are at increased risk of developing de novo post-transplant malignancies (PTMs), with regional differences in types with excess risk compared to the general population. A single-center, population-controlled, retrospective cohort study was conducted at a tertiary care center in Thailand among all adults who underwent their first kidney transplant from 1986 to 2018. Standardized incidence ratios (SIRs) of malignancy by age, sex, and place of residence were obtained using data from the National Cancer Registry of Thailand as population control. There were 2,024 KTRs [mean age, 42.4 years (SD 11.4); female patients, 38.6%] during 16,495 person-years at risk. Of these, 125 patients (6.2%) developed 133 de novo PTMs. The SIR for all PTMs was 3.85 (95% CI 3.22, 4.56), and for pooled solid and hematologic PTMs, it was 3.32 (95% CI 2.73, 3.99). Urothelial malignancies had the largest excess risk, especially in women [female SIR 114.7 (95% CI 66.8, 183.6); male SIR 17.5 (95% CI 8.72, 31.2)]. The next two most common cancers were non-Hodgkin's lymphoma and skin cancer [SIR 20.3 (95% CI 13.6, 29.1) and 24.7 (95% CI 15.3-37.8), respectively]. Future studies are needed to identify the risk factors and assess the need for systematic screening among PTMs with excess risk in KTRs.

The Prevalence and Risk Factors of Hyperkalemia in the Outpatient Setting.

Background: Hyperkalemia is a life-threatening condition in outpatient and emergency departments. Hyperkalemia is associated with more events of major adverse cardiovascular diseases, hospitalization, and death. The aim of this study is to study and assess the prevalence and risk factors for developing hyperkalemia within the Thai population. Method: A cross-sectional observational study of 3,299 unique adult patients (≥18 years) in one calendar year (2021) with at least 1 valid serum potassium (SK) test was conducted in the outpatient department of medicine. Hyperkalemia was determined as SK ≥5.8 mmol/L without hemolysis or technical error. Clinical data and laboratory tests were collected for analysis of risk factors. Result: 2,971 patients (131 hyperkalemia and 2,840 control) were eligible. The annual prevalence of hyperkalemia was 4.41%. The mean ages of patients were 66.5 years in the hyperkalemia group and 55.9 years in the control group. Increasing age had a positive association (r = 0.220, p < 0.001) to risk of hyperkalemia, whereas the estimated glomerular filtration rate (eGFR) had an inverse association with SK level (r = -0.398, p < 0.001). The risk factors for hyperkalemia were patients with age ≥65 years (odds ratio, 2.106; 95% CI, 1.399, 3.171; p < 0.001), presence of diabetes mellitus (DM, odds ratio, 1.541; 95% CI, 1.030, 2.306; p = 0.036), chronic kidney disease (CKD) stage ≥3 (odds ratio, 14.885; 95% CI, 8.112, 27.313; p < 0.001), hemodialysis treatment (odds ratio, 10.170; 95% CI, 5.858, 17.657; p < 0.001), and usage of renin-angiotensin-aldosterone system inhibitors (RAASi, odds ratio, 2.256; 95% CI, 1.440, 3.536; p < 0.001). Conclusion: The risk factors contributing to hyperkalemia were patients with older age, DM, CKD, hemodialysis treatment, and usage of RAASi. Although the usage of RAASi is proven to be a cardiovascular advantage in the elderly, DM, and CKD patients, careful monitoring of SK is strongly advised to optimize patient care.

Establishment and Characterization of MUi027-A: A Novel Patient-Derived Cell Line of Polycystic Kidney Disease with PKD1 Mutation.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent genetic diseases affecting the kidneys. A genetically specific mutation model is required to comprehend its pathophysiology and to develop a drug treatment. In this study, we successfully developed human induced pluripotent stem cells (hiPSCs) named MUi027-A from skin fibroblasts of a patient diagnosed with ADPKD and carrying the PKD1 frameshift mutation (c.7946_7947delCT). MUi027-A cells showed the same genetic fingerprints as the parental cells, including the presence of the PKD1 mutation. MUi027-A hiPSCs displayed embryonic stem cell-like characteristics with the capability of differentiating into the three germ layers. Upon directed differentiation, MUi027-A hiPSCs could be differentiated into tubular organoids with the expression of renal cell markers. Furthermore, we compared the efficiency of cyst formation in two human iPSC lines with different PKD1 mutations. When cyst formation was induced by either forskolin or blebbistatin, MUi027-A hiPSC-derived kidney organoids displayed higher frequencies of cyst formation when compared to organoids generated from an iPSC cell line with non-truncating PKD1 mutation genotype (c.5878C > T), suggesting the presence of physiological differences in the mechanism of cyst formation between different PKD1 mutants. Overall, we generated and characterized a novel human iPSC line with a specific PKD mutation and demonstrated its potential as a disease model to study the pathophysiology of genetic determinants in the development of ADPKD disease.

Distribution pattern of mesangial C4d deposits as predictor of kidney failure in IgA nephropathy.

Mesangial C4d deposits have been associated with worse outcomes in Western patients with IgA nephropathy (IgAN), but there is limited data in Asians. Previously, a high proportion of stained glomeruli was often required for the classification of C4d positive (C4d+ve). Positive staining in lower proportion of staining would be classified as C4d-ve. This retrospective study evaluated the prognostic value of C4d+ve using a less stringent definition (one C4d+ve glomerulus) in Thai patients with IgAN (n = 120). Baseline findings and outcomes were compared between those with more extensive C4d staining patterns and those with more restricted staining. Clinico-pathologic parameters and risk for kidney outcomes (kidney failure or decline GFR50%) were compared between C4d+ve versus C4d-ve, and between different patterns: Focal (< 50%) versus Diffuse (≥ 50% of glomeruli); or Global (≥ 50) versus Segmental (< 50% of mesangial area). The hazard ratios were estimated using Cox proportional hazard models for Model 1 (Oxford score+ C4d) and Model 2 (Model 1+ clinical factors). C4d+ve (n = 81) had lower eGFR, more global sclerosis, and interstitial fibrosis than C4d-ve at baseline. The 5-year kidney survival for C4d+ve was lower (53.7%) than C4d-ve (89.7%); P = 0.0255. By univariate analysis, T1, T2, C4d+ve, eGFR<60, proteinuria were predictors of kidney outcome. By multivariate analysis, proteinuria, T1, T2 and C4d+ve were independent predictors (Model 2 HR (95% CI) C4d+ve: 3.24 (1.09-9.58), p = 0.034). Segmental had lower eGFR, higher tubulointerstitial fibrosis, and segmental sclerosis compared to Global pattern. Clinicopathological parameters were not different between Focal and Diffuse patterns. Outcomes were similar between staining patterns. In conclusion, C4d staining may be a valuable marker of poor prognosis in Asian patients with IgAN. Less stringent criteria for C4d+ve should be considered as no differences in outcomes were observed between more extensive staining with less extensive patterns. More studies are needed to identify the optimum criteria for C4d+ve.

The correlation between kidney volume and measured glomerular filtration rate in an Asian ADPKD population: a prospective cohort study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder that leads to end stage renal disease (ESRD). Cyst expansion in ADPKD is strongly associated with the decline in renal function. However, the correlation between total kidney volume (TKV) and glomerular filtration rate (GFR) at an early stage has not been well demonstrated. There is growing evidence that utilization of estimated GFR (eGFR) may induce misleading information in a population with near normal renal function. Therefore, a more accurate method is essential. METHODS: A prospective cohort of ADPKD patients was conducted with clinical data and laboratory collection. Measured GFR (mGFR) was assessed by iohexol plasma clearance method using ultra performance liquid chromatography. eGFR was calculated using the CKD-EPI equation. Kidney volumes were evaluated using MRI imaging protocol. RESULTS: Thirty two patients completed the study. The mean age was 56 years old. The mean initial mGFR was 83.8 mL/min/1.73m2. The mean change in mGFR per year was -2.99 mL/min/1.73m2/year. The mean initial height-adjusted TKV (htTKV) was 681.0 mL/m. The mean percentage change in htTKV per year (%ΔhtTKV/y) was 4.77 %/year. mGFR had a better association with clinical parameters than eGFR. Initial mGFR was significantly and inversely correlated with initial htTKV and age. The percentage change in mGFR per year was significantly and inversely correlated with the %ΔhtTKV/y and 24-hr urine albumin. The %ΔhtTKV/y was significantly correlated with initial htTKV. CONCLUSIONS: Our studies demonstrated that mGFR using iohexol is a more reliable and accurate method than eGFR for evaluating GFR changes in the early stages of ADPKD patients. There is a strong inverse correlation between kidney volume and mGFR in an Asian ADPKD population. The initial htTKV is a good predictor of kidney volume progression. The %ΔhtTKV/y is a good early surrogate marker for the decline in renal function. 24-hr urine albumin is also a good indicator for renal progression.

Generation of human induced pluripotent stem cell line (MUi026-A) from a patient with autosomal dominant polycystic kidney disease carrying PKD1 point mutation.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the common genetic kidney disorders that are caused by mutations in PKD1 or PKD2 gene. In this report, the MUi026-A human induced pluripotent stem cell (hiPSC) line was established from the skin fibroblasts of a female ADPKD patient who had the PKD1 mutation with c.5878C > T. The iPSC line retained normal karyotype. The cells displayed embryonic stem cell-like characteristics with pluripotency marker expression and were able to differentiate into three germ layers.

Abdominal aorta and pelvic artery calcifications on plain radiographs may predict mortality in chronic kidney disease, hemodialysis and renal transplantation.

PURPOSE: Vascular calcification is common in chronic kidney disease (CKD) and predicts poor patient outcomes. While computed tomography is the gold standard for evaluation of vascular calcification, plain radiograph offers a simpler and less costly alternative. The calcification of abdominal aorta, iliac and femoral arteries has been evaluated by plain radiograph, but the data on their outcome predictabilities are still limited. The present study investigated the role of abdominal aortic calcification (AAC) and pelvic arterial calcification (PAC) in predicting overall morality in non-dialysis CKD stages 2-5 (CKD 2-5), maintenance hemodialysis (HD) and long-term kidney transplant (KT) patients. METHODS: Four hundred and nineteen patients were included. Lateral abdominal and pelvic radiographs were obtained. The degree of AAC and PAC was evaluated according to the methods described previously by Kaupplia et al. and Adragao et al. Patients were followed prospectively for 5 years. RESULTS: AAC and PAC scores correlated well with the correlation coefficients of 0.442 for CKD 2-5, 0.438 for HD and 0.586 for KT (p < 0.001). Patients with AAC score > 6 or PAC score > 1 were older, showed higher prevalence of DM and had higher serum phosphate and PTH but lower serum albumin and eGFR. A more severe degree of AAC was associated with an increase in KT duration, whereas a more severe degree of PAC was associated with worsening kidney function and prolonged dialysis vintage. Kaplan-Meier survival curves revealed AAC score > 6 as a significant predictor of all-cause mortality in CKD 2-5 but not in HD or KT, whereas PAC score > 1 was a significant predictor of all-cause mortality in all three populations. After adjusting for age, the predictability of AAC was lost, whereas PAC remained an independent predictor of mortality in all three populations. Adjustments for cardiovascular and CKD risk factors including age, gender, BMI, DM, serum albumin, calcium and phosphate attenuated the predictability of PAC in HD but not in CKD 2-5 or KT patients. CONCLUSION: PAC was better than AAC in predicting mortality in CKD, HD and KT patients.

Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B.

AIMS: Proximal renal tubular dysfunction (PRTD) is an infrequent complication after nucleotide analogue therapy. We evaluated the outcomes of PRTD and nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB). METHODS: A longitudinal follow-up study was performed in patients with PRTD after nucleotide analogue discontinuation. Serum and urine were collected at baseline and every 3 months for one year. The fractional excretion of phosphate (PO4), uric acid (UA), and potassium and tubular maximal reabsorption rate of PO4 to glomerular filtration rate (TmPO4/GFR) were calculated. Renal losses were defined based on the criteria of substance losses. Subclinical PRTD and overt PRTD were diagnosed when 2 and ≥3 criteria were identified. RESULTS: Eight subclinical and eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal, there were overall improvements in GFR, serum PO4, and UA. Renal loss of PO4, UA, protein, and ß2-microglobulin reduced over time. At one year, complete reversal of PRTD was seen in 13 patients (81.2%). Improvements in PRTD were seen in all but one patient. CONCLUSION: One year after nucleotide analogue withdrawal, PRTD was resolved in most patients. Changes in TmPO4/GFR, urinary protein, and ß2-microglobulin indicate that urinary biomarkers may represent an early sign of PRTD recovery.

Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term Treatment of Chronic Hepatitis B: A Cross-Sectional Study.

Background. There have been few reports of nucleotide analogue-related renal tubular dysfunction (RTD) in CHB patients. We assessed the prevalence and presentation of nucleotide analogue-related proximal RTD. Methods. A cross-sectional study was performed in CHB patients taking nucleotide analogues. Inclusion criteria were patients who were on adefovir or tenofovir as mono- or add-on therapy with lamivudine (LAM) >1 year. Serum and urine were collected. Fractional excretion of phosphate (FEPO4), uric acid (FEUA), and potassium was calculated. Renal losses were defined based on the criteria: protein (24-hour urine protein >150 mg), glucose (glycosuria with normoglycemia), phosphate (FEPO4 >18%), uric acid (FEUA >15%), potassium (renal potassium losses with hypokalemia), and bicarbonate (normal gap acidosis). Subclinical and overt proximal RTD were defined when 2 and ≥3 criteria presented. Results. Ninety-two patients were enrolled. The mean duration of nucleotide analogue taking was 55.1 ± 29.6 months. Proximal RTD was found in 24 (26.1%) patients (subclinical 15 (16.3%) and overt 9 (9.8%)). The severity of RTD was associated with the duration of nucleotide analogue (P = 0.01). Conclusions. The prevalence of proximal RTD in CHB patients taking nucleotide analogues was 26%. The severity of RTD was associated with the treatment duration. Comprehensive testing is necessary for early detecting nucleotide analogue-related nephrotoxicity.

Effects of Therapy on Urine Neutrophil Gelatinase-Associated Lipocalin in Nondiabetic Glomerular Diseases with Proteinuria.

Urine neutrophil gelatinase-associated lipocalin (NGAL) is widely used as a biomarker for acute kidney injury. Cross-sectional studies have shown that NGAL may be elevated in glomerular diseases, but there is limited information on the value of NGAL in predicting treatment response or on the changes of NGAL levels after therapy. We prospectively evaluated the effects of therapy on NGAL in nondiabetic glomerular diseases. Urine NGAL was collected at biopsy and follow-up at 12 months. At baseline, NGAL in glomerular disease patients (n = 43) correlated with proteinuria, but not with glomerular filtration rate (GFR). After therapy with renin-angiotensin blockers and/or immune modulating agents, change of NGAL correlated with change of proteinuria, but not with change of GFR. NGAL at baseline was not different between patients in complete remission (CR) at follow-up compared to those not in remission (NR). Compared to baseline, NGAL at follow-up decreased in CR (n = 10), but not in NR. Change of NGAL was greater in CR than NR. In conclusion, the change of urine NGAL correlated with the change of proteinuria. Baseline NGAL was not a predictor of complete remission. Future studies will be necessary to determine the role of NGAL as a predictor of long term outcome in proteinuric glomerular diseases.

Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation.

PURPOSE: The purpose of this study is to determine the impacts of CYP3A5 polymorphism on tacrolimus concentration and the proportion of patients within a target therapeutic range during the first week after transplantation together with the 3-month acute rejection rate in kidney transplant patients receiving a minimized tacrolimus regimen. METHODS: A total of 164 patients participated in the study. All received oral tacrolimus twice daily starting on the day of surgery with the target pre-dose (trough) concentration of 4-8 ng/ml for prevention of allograft rejection. Cytochrome P450 (CYP) 3A5 genotypes were determined. The patients were divided into CYP3A5 expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (homozygous CYP3A5*3). Whole blood tacrolimus concentrations on days 3 and 7 posttransplantation and the incidence of biopsy-proven acute rejection (BPAR) at 3-month posttransplantation were compared between groups. RESULTS: On day 3, the median (IQR) dose-and-weight-normalized trough concentration in expressers and nonexpressers were 54.61 (31.98, 78.87) and 91.80 (57.60, 130.20) ng/ml per mg/kg/day, respectively (p < 0.001). Although only 47 and 42% of expressers and nonexpressers were within the target range on day 3, approximately 60% of both groups were within the target range on day 7. Proportions of BPAR among expressers and nonexpressers were 6.0 and 7.4 %, respectively (p = 0.723). The median (IQR) times to the first rejection in CYP3A5 expressers and nonexpressers were 32 (12, 68) and 15 (12, 37) days, respectively (p = 0.410). CONCLUSIONS: Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP3A5 polymorphism on BPAR was not observed in this study.

Propylthiouracil-associated rapidly progressive crescentic glomerulonephritis with double positive anti-glomerular basement membrane and antineutrophil cytoplasmic antibody: the first case report.

We report a case of propylthiouracil (PTU)-induced double antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM antibody) disease causing pulmonary-renal syndrome in a 35-year-old Thai woman with 10-year history of PTU treatment for thyrotoxicosis. She developed clinical symptoms of vasculitis upon receiving long-term PTU treatment. Prednisolone treatment and the switching from PTU to methimazole resulted to short-term clinical improvement. Nevertheless following termination of steroid treatment, she developed recurrent pulmonary hemorrhage and rapidly progressive glomerulonephritis. The kidney biopsy showed crescentic glomerulonephritis with linear IgG deposit on the glomerular basement membrane although transbronchial lung biopsy showed no immune deposit along the alveolar basement membrane. Serum testing for p-ANCA was positive and western blot showed positive antibody to the alpha-3 chain of collagen type IV. Both ANCA and anti-GBM antibody may play a role in the development of end organ damage. To facilitate early and specific intervention, clinicians should be aware of the propensity of PTU to cause lupus-like syndromes with renal involvement. In patients with PTU-induced ANCA-associated glomerulonephritis, serum anti-GBM antibody test may be useful in the early diagnosis of double positive antibodies disease and plasmapheresis should be performed without delay.

Low hip bone mineral density predicts mortality in maintenance hemodialysis patients: a five-year follow-up study.

BACKGROUND: Bone loss is common among hemodialysis patients and contributes to mortality. The association between bone loss and vascular calcification may explain the increased mortality risk. Studies on the association between decreased bone mass and mortality in maintenance hemodialysis patients are limited. METHODS: Eighty-three hemodialysis patients underwent bone mineral density (BMD) and coronary artery calcification (CAC) measurements. The relationship between BMD and mortality was analyzed after a 5-year follow-up period. RESULTS: Eighty percent of the patients had reduced hip BMD. In univariate Cox regression analyses, age, cardiovascular disease, dyslipidemia, increased CAC score, increased comorbidity score and decreased hip BMD were associated with mortality. Low hip BMD remained independently associated with mortality after adjustments for cardiovascular risk factors, comorbidity score and CAC score. Patients with BMD in the lowest tertile had the worst survival. CONCLUSION: Low hip BMD predicted mortality in maintenance hemodialysis patients independent of CAC.

Vascular calcification in long-term kidney transplantation.

AIM: Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. METHODS: The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. RESULTS: The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. CONCLUSIONS: Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.

Long-term effectiveness of acetazolamide on permanent weakness in hyperkalemic periodic paralysis.

Acetazolamide is commonly used as an empirical treatment for inherited periodic paralyses although some patients may develop deleterious effects. We report a 65 year-old man with hyperkalemic periodic paralysis and late-onset permanent weakness in association with the common T704M mutation in α-subunit, skeletal muscle voltage-gated sodium channel gene. He rapidly recovered from weakness after acetazolamide treatment. Magnetic resonance imaging of thighs comparing pre- and post-treatment revealed a significant increase in muscle bulk. The patient has been without any type of weakness for over 6 years. This data show the remarkable benefit of acetazolamide on permanent weakness of hyperkalemic periodic paralysis in association with the T704M mutation.

The added-up albumin enhances the diuretic effect of furosemide in patients with hypoalbuminemic chronic kidney disease: a randomized controlled study.

BACKGROUND: Chronic kidney disease (CKD) with edema is a common clinical problem resulting from defects in water and solute excretion. Furosemide is the drug of choice for treatment. In theory, good perfusion and albumin are required for the furosemide to be secreted at the tubular lumen. Thus, in the situation of low glomerular filtration rate (GFR) and hypoalbuminemia, the efficacy of furosemide alone might be limited. There has been no study to validate the effectiveness of the combination of furosemide and albumin in this condition. METHODS: We conducted a randomized controlled crossover study to compare the efficacy of diuretics between furosemide alone and the combination of furosemide plus albumin in stable hypoalbuminemic CKD patients by measuring urine output and sodium. The baseline urine output/sodium at 6 and 24 hours were recorded. The increment of urine output/sodium after treatment at 6 and 24 hours were calculated by using post-treatment minus baseline urine output/sodium at the corresponding period. RESULTS: Twenty-four CKD patients (GFR = 31.0 ± 13.8 mL/min) with hypoalbuminemia (2.98 ± 0.30 g/dL) were enrolled. At 6 hours, there were significant differences in the increment of urine volume (0.47 ± 0.40 vs 0.67 ± 0.31 L, P < 0.02) and urine sodium (37.5 ± 29.3 vs 55.0 ± 26.7 mEq, P < 0.01) between treatment with furosemide alone and with furosemide plus albumin. However, at 24 hours, there were no significant differences in the increment of urine volume (0.49 ± 0.47 vs 0.59 ± 0.50 L, P = 0.46) and urine sodium (65.3 ± 47.5 vs 76.1 ± 50.1 mEq, P = 0.32) between the two groups. CONCLUSION: The combination of furosemide and albumin has a superior short-term efficacy over furosemide alone in enhancing water and sodium diuresis in hypoalbuminemic CKD patients. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registration (ANZCTR12611000480987).

Prevalence trend of renal replacement therapy in Thailand: impact of health economics policy.

OBJECTIVE: The national health insurance fund in Thailand initiated by the national health security act in November, 2002. In October 2007, the national health insurance fund launched the first renal replacement therapy (RRT) reimbursement plan by the "Peritoneal Dialysis-First" (PD First) policy. The rationale of the PD First Policy resulted from the perspective that PD for end stage renal disease (ESRD) treatment offers the most economic and efficient outcome. The present study was conducted to determine whether the increase of RRT penetration by national health policy could impact the national RRT prevalence. MATERIAL AND METHOD: The Thailand Renal Replacement Therapy (TRT) database in 2007, 2008, and 2009 were retrieved and analyzed. RESULTS: By TRT registry data, the total yearly prevalence of RRT increased by an average of 14.8% after the implementation of national health insurance and the "PD First" policy from 2007 to 2009. The total yearly prevalence of hemodialaysis (HD) modestly increased (14.7%) while the total yearly prevalence of PD remarkably expanded by 107.3%. The yearly incidence of all RRT modalities increased by an average of 34.8% in 2007 to 2009. The yearly incidence of HD modestly increased (8.1%) while the total yearly incidence of PD remarkably elevated by 157.8%. Civil Servants Medical Benefit Compensation (CSMBS) was the major funding source of RRT cases (34.5%) while national health insurance funding was the second major funding source (26.0%). From 2007-2009, the CSMBS funding was the majority of HD while national health insurance funding was the majority of PD. The sharing of PD by national health insurance increased from 33.9% in 2007, 58.6% in 2208, and 77.2% in 2009. CONCLUSION: The coverage ofESRD patients by national health insurance fund by the "PD First" policy impacted the RRT prevalence and incidence both the total prevalence and total incidence due to the universal penetration to RRT treatment of Thai population. Also, the policy altered the RRT modality predisposition. PD modality willfinally be the majority ofThaiRRT modalities if the policy can be managed successfully.

Aldosterone increases Na+ -K+ -ATPase activity in skeletal muscle of patients with Conn's syndrome.

OBJECTIVE: In Conn's syndrome, hypokalaemia normally results from renal potassium loss because of the effect of excess aldosterone on Na(+) -K(+) -ATPase in principal cells. Little is known about the effect of aldosterone on cellular potassium redistribution in skeletal muscle. Our study determined the effect of aldosterone on muscle Na(+) -K(+) -ATPase. DESIGN: Muscle biopsies were taken from six patients immediately before and 1 month after adrenalectomy. Ten age-matched subjects with normal levels of circulating aldosterone served as controls. RESULTS: Average plasma aldosterone was significantly higher in presurgery (235·0 ± 51·1 pg/ml) than postsurgery (64·5 ± 25·1 pg/ml) patients. Similarly, Na(+) -K(+) -ATPase activity, relative mRNA expression of α(2) (not α(1) or α(3) ) and ß(1) (not ß(2) or ß(3) ), and protein abundance of α(2) and ß(1) subunits were greater in pre- than postsurgery samples (128·7 ± 12·3 vs 79·4 ± 13·3 nmol·mg/protein/h, 2·45 ± 0·31 vs 1·04 ± 0·17, 1·92 ± 0·22 vs1·02 ± 0·14, 2·17 ± 0·33 vs 0·98 ± 0·09 and 1·70 ± 0·17 vs 0·90 ± 0·17, respectively, all P<0·05). The activity and mRNA expression of the α(2) and ß(1) subunits correlated well with plasma aldosterone levels (r = 0·71, r = 0·75 and r = 0·78, respectively, all P < 0·01). CONCLUSIONS: Our study provides the first evidence in human skeletal muscle that increased plasma aldosterone leads to increased Na(+) -K(+) -ATPase activity via increases in α(2) and ß(1) subunit mRNAs and their protein expressions. The increased activity may contribute in part to the induction of hypokalaemia in patients with Conn's syndrome.

Urine potassium per hour as a marker for renal potassium losses.

BACKGROUND: Hypokalemia, serum potassium (K) < 3.5 mEq/L, is a serious and common clinical problem. The traditional diagnosis of renal potassium losses is 24-hr urine potassium (24U(K)) > or = 20 mEq/day during hypokalemia. Immediate replacement of potassium is often required to prevent complication but may normalize serum K during 24-hr urine collection and render the test inconclusive. MATERIAL AND METHOD: The authors examined the ability of urinary indices including 24U(K), transtubular potassium gradient (TTKG), fractional excretion of potassium (FE(K)), urine potassium-creatinine ratio (U(K/Cr)) and spot U(K) and introduced urine potassium per hour during the first 8 hours (U(K)/hr) as a novel index for evaluation of hypokalemia during treatment. Any serum K level > or = 4 mEq/L during urine collection was defined as normalized serum K. In the present study, the final classification of renal K losses in non-normalized 24-hr serum K group was made when 24U(K) > or = 20 mEq/day. In normalized group, the final classification of renal or non-renal K losses was based on the majority of the results of four urine indices including TTKG, FE(K) U(K/Cr) and spot U(K). RESULTS: Of 61 patients (renal:non-renal = 50:11), 51% and 18% met the criteria of normalized 24-hr and 8-hr serum K. Over all, the U(K)/hr > or = 0.9 mEq/hr can indicate renal K losses with a sensitivity of 96% and specificity of 72.7% compared with the 24U(K) > or = 20 mEq/day of 100% and 54.5%, respectively. In a subgroup of normalized 24-hr serum K, the sensitivity and specificity of U(K)/hr = 95.5% and 77.8% whereas 24U(K) = 100% and 44.4%, respectively CONCLUSION: U(K)/hr is a new practical, simple, and reliable marker that can be applied to evaluate hypokalemic patients during treatment with comparable sensitivity and specificity with 24U(K).