The association of tumor necrosis factor superfamily 13 with recurrence of immunoglobulin A nephropathy in living related kidney transplantation.

BACKGROUND: An increasing amount of evidence has demonstrated an association between an increase in the level of tumor necrosis factor superfamily 13 (TNFSF13) and immunoglobulin A nephropathy (IgAN) progression. We aimed to evaluate if the level of pre-transplant serum TNFSF13 is predictive of IgAN recurrence after kidney transplantation. METHODS: This analysis was based on the clinical and laboratory data of 69 patients with IgAN who underwent first kidney transplantation with no evidence of mesangial IgA deposits in zero-time transplantation biopsy. We measured pre-transplant serum TNFSF13, total IgA, and galactose-deficient IgA1 levels. RESULTS: The recurrence rate of IgAN over a median follow-up duration of 5.1 years was 15.9% (11/69 patients), with a mean time to the first recurrence of 1.7 years. The high pre-transplant TNFSF13 level was associated with IgAN recurrence after kidney transplantation among patients who received a graft from a living related donor. CONCLUSIONS: This study highlights association of TNFSF13 levels in recurrent IgAN patients who undergo living related donor transplantation. Further research is needed to clarify mechanisms by which TNFSF13 affects the recurrence of IgA nephropathy.

Autologous arteriovenous fistula is associated with superior outcomes in elderly hemodialysis patients.

BACKGROUND: The number of elderly patients with end-stage renal disease is increasing rapidly. The higher prevalence of comorbidities and shorter life expectancy in these patients make it difficult to decide on the type of vascular access (VA). We explored the optimal choice for VA in elderly hemodialysis patients. METHODS: We included elderly patients (> 65 years) visiting our VA clinic and divided them into three groups as follows: radiocephalic arteriovenous fistula (AVF), brachiocephalic AVF, and prosthetic arteriovenous graft (AVG). The primary outcomes were VA abandonment and all-cause mortality. The secondary outcome was maturation failure (MF). RESULTS: Of 529 patients, 61.2% were men. The mean age was 73.6 ± 6.0 years. The VA types were as follows: 49.9% radiocephalic AVF, 31.8% brachiocephalic AVF, and 18.3% AVG. Patients with an AVG tended to be older, female, and have a lower body mass index. More than half of patients (n = 302, 57.1%) started dialysis with central catheters, but the proportion of predialysis central catheter placement was not different among the VA types. Radiocephalic AVF was significantly superior to AVG in terms of VA abandonment (P = 0.005) and all-cause mortality (P < 0.001) in spite of a higher probability of MF. Brachiocephalic AVF was associated with a shorter time to the first needling and fewer interventions before maturation than radiocephalic AVF. CONCLUSIONS: Autologous AVF was suggested as the preferred VA choice in terms of long-term outcomes in elderly patients.

Genome-wide association analysis identifies multiple loci associated with kidney disease-related traits in Korean populations.

Chronic kidney disease (CKD) is an important social health problem characterized by a decrease in the kidney glomerular filtration rate (GFR). In this study, we analyzed genome-wide association studies for kidney disease-related traits using data from a Korean adult health screening cohort comprising 7,064 participants. Kidney disease-related traits analyzed include blood urea nitrogen (BUN), serum creatinine, estimated GFR, and uric acid levels. We detected two genetic loci (SLC14A2 and an intergenic region) and 8 single nucleotide polymorphisms (SNPs) associated with BUN, 3 genetic loci (BCAS3, C17orf82, ALDH2) and 6 SNPs associated with serum creatinine, 3 genetic loci (BCAS3, C17orf82/TBX2, LRP2) and 7 SNPs associated with GFR, and 14 genetic loci (3 in ABCG2/PKD2, 2 in SLC2A9, 3 in intergenic regions on chromosome 4; OTUB1, NRXN2/SLC22A12, CDC42BPG, RPS6KA4, SLC22A9, and MAP4K2 on chromosome 11) and 84 SNPs associated with uric acid levels. By comparing significant genetic loci associated with serum creatinine levels and GFR, rs9895661 in BCAS3 and rs757608 in C17orf82 were simultaneously associated with both traits. The SNPs rs11710227 in intergenic regions on chromosome 3 showing significant association with BUN is newly discovered. Genetic variations of multiple gene loci are associated with kidney disease-related traits, and differences in associations between kidney disease-related traits and genetic variation are dependent on the population. The meanings of the mutations identified in this study will need to be reaffirmed in other population groups in the future.

Update of aristolochic acid nephropathy in Korea.

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSION: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

Effects of colchicine on renal fibrosis and apoptosis in obstructed kidneys.

BACKGROUND/AIMS: Colchicine is an established drug for microtubule stabilization that may reduce tissue injury. No data were available that its effects may depend on the dosage of colchicine. We investigated the anti-fibrotic and apoptotic effects of various dose of colchicine in a unilateral ureteral obstruction (UUO) model. METHODS: Thirty-six Sprague-Dawley rats were randomly assigned into six groups. Two sham groups were divided into a vehicle-treated or colchicine-treated group (100 µg/kg/day). Four UUO groups were treated with either vehicle or three different doses of colchicine for 7 days (30, 60, and 100 µg/kg/day, intraperitoneally). All of the animals were sacrificed on day 7. RESULTS: Colchicine treatment diminished acetylated α-tubulin and tumor growth factor-ß immunoreactivities in the cortical area of the 7-day obstructed kidneys, which was in dose dependent manner. Colchicine attenuated tubulointerstitial damage and apoptosis in both cortical and medullary area, and beneficial effects of colchicine therapy were dramatically shown at the higher dosage of colchicine. The expression levels of cleaved caspase-3, ED-1, and fibronectin were decreased in UUO animals. CONCLUSIONS: We found that the proper dosage of colchicine may have anti-fibrotic and anti-apoptotic effects in obstructed kidneys. For clinical applications, an optimal dose of colchicine should be evaluated to maximize the prevention of renal disease progression.

Body fat distribution is more predictive of all-cause mortality than overall adiposity.

AIMS: The relationship between directly measured body fat and all-cause mortality has been rarely studied. The aim of this study was to evaluate the predictive significance of computed tomography (CT)-measured body fat, including both visceral fat area (VFA) and subcutaneous fat area (SFA), for mortality. METHODS: The study included 36 656 participants who underwent abdominal CT as part of a health check-up at a single university-affiliated healthcare center in 2007 to 2015. Of those, 32 593 participants with data regarding vital status as of May 2016 were included in the final analysis. The main factors evaluated were VFA, SFA and visceral-to-subcutaneous fat area ratio (VSR), and the primary outcome was all-cause mortality. RESULTS: There were 253 deaths during a mean follow-up of 5.7 years. Increased SFA was associated with decreased all-cause mortality, whereas an increased VFA and VSR were related to increased all-cause mortality. Compared with the predictive power of body mass index (BMI), SFA and VSR showed a larger area under the curve than did BMI. In Kaplan-Meier survival curve analysis, increased SFA and VSR were associated with decreased and increased hazard of all-cause death, respectively. However, in multivariate Cox proportional hazard regression analysis, only VSR was independently associated with all-cause mortality. Moreover, this relationship was paralleled by the harmful impact of increased VSR on metabolic profiles. CONCLUSION: Increased VSR was an independent predictor of all-cause mortality. This suggests that the location of fat deposits may be more important than the actual amount of body fat.

Elevated baseline potassium level within reference range is associated with worse clinical outcomes in hospitalised patients.

The clinical significance of elevated baseline serum potassium (K+) levels in hospitalised patients is rarely described. Hence, we performed a retrospective study assessing the significance of elevated K+ levels in a one-year admission cohort. Adult patients without hypokalaemia or end-stage renal disease were included. Adverse outcomes were all-cause mortality, hospital-acquired acute kidney injury, and events of arrhythmia. In total, 17,777 patients were included in the study cohort, and a significant difference (P < 0.001) was observed in mortality according to baseline serum K+ levels. The adjusted hazard ratios (HRs) and associated 95% confidence intervals (CIs) of all-cause mortality for K+ levels above the reference range of 3.6-4.0 mmol/L were as follows: 4.1-4.5 mmol/L, adjusted HR 1.075 (95% CI 0.981-1.180); 4.6-5.0 mmol/L, adjusted HR 1.261 (1.105-1.439); 5.1-5.5 mmol/L, adjusted HR 1.310 (1.009-1.700); >5.5 mmol/L, adjusted HR 2.119 (1.532-2.930). Moreover, the risks of in-hospital acute kidney injury and arrhythmia were higher in patients with serum K+ levels above 4.0 mmol/L and 5.5 mmol/L, respectively. In conclusion, increased serum K+ levels, including mild elevations may be related to worse prognosis. Close monitoring and prompt correction of underlying causes or hyperkalaemia itself is warranted for admitted patients.

Hydrochlorothiazide does not increase furosemide's effects in end-stage renal disease.

Diuretic therapy for the treatment of edema in patients with end-stage renal disease (ESRD) is unsatisfactory, and a combination of thiazide and loop diuretics may produce better clinical effects. To evaluate the influence of thiazide on loop diuretic therapy for ESRD, we performed a crossover study of furosemide versus hydrochlorothiazide plus furosemide treatment. The diuretic effects of furosemide (160 mg i.v.) alone versus a combination of hydrochlorothiazide (100 mg p.o.) and furosemide were studied in ten ESRD patients with proteinuria greater than 1 g/day. The diuretic effects were compared for 24 h urine volume and electrolyte excretion. To detect the influence of thiazide that may have been obscured in the widely dispersed data, pharmacodynamic analysis of urine furosemide excretion rate versus fractional excretion of sodium (FeNa) was also performed using mixed-effect modeling. Combination therapy was not significantly different from furosemide monotherapy in terms of 24 h urine volume, chloride, or sodium excretion. Hydrochlorothiazide was not a significant covariate in the furosemide effect for the pharmacodynamic model. In patients with ESRD and severe proteinuria (>1,000 mg/day), the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furosemide.

Recurrent Vascular Access Dysfunction as a Novel Marker of Cardiovascular Outcome and Mortality in Hemodialysis Patients.

BACKGROUND: Vascular access (VA) is essential for hemodialysis (HD) patients, and its dysfunction is a major complication. However, little is known about outcomes in patients with recurrent VA dysfunction. We explored the influence of recurrent VA dysfunction on cardiovascular (CV) events, death and VA abandonment. METHODS: This is a single-center, retrospective study conducted in patients who underwent VA surgery between 2009 and 2014. VA dysfunction was defined as VA stenosis or thrombosis requiring intervention after the first successful cannulation. Patients with ≥2 interventions within 180 days were categorized as having recurrent VA dysfunction. Outcomes were analyzed using Cox proportional hazards model before and after propensity score matching. RESULTS: Of 766 patients (ages 59.6 ± 14.3 years, 59.7% male), 10.1% were in the recurrent VA dysfunction group. Most baseline parameters after matching were similar between the recurrent and non-recurrent groups. A total of 213 propensity score-matched patients were followed for 28.7 ± 15.8 months, during which 46 (21.6%), 30 (14.1%) and 14 (6.6%) patients had de novo CV outcomes, died and abandoned VA, respectively. Recurrent VA dysfunction after adjustment remained an independent risk factor for CV events (adjusted hazards ratio (aHR), 2.71; 95% CI 1.48-4.98; p = 0.001). Moreover, recurrent VA dysfunction predicted composite all-cause mortality (ACM)/CV events (aHR 1.99; 95% CI 1.21-3.28; p = 0.007). CONCLUSIONS: Recurrent VA dysfunction was a novel independent risk factor for CV and composite ACM/CV events in HD patients, but not for VA abandonment. Patients with recurrent vascular dysfunction should be carefully monitored not only for VA patency but also for CV events.

Erratum: Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome.

[This corrects the article on p. 47 in vol. 31, PMID: 26770037.].

NT-proBNP Is Predictive of the Weaning from Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) is a dialysis modality used to treat patients with severe acute kidney injury. Nevertheless, there is limited information on the predictors of weaning from CRRT. The present study examined whether the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) can predict weaning from CRRT, based on the fact that this cardiac neurohormone is known to predict kidney dysfunction. Plasma NT-proBNP and several other baseline parameters at the time of starting CRRT were retrieved from 160 patients. The odds ratio (OR) for weaning from the CRRT within two weeks was calculated using a multivariate stepwise logistic model. We calculated the cut off value predicting weaning outcome by using the receiver operating characteristic curve and corresponding Youden index, and then divided patients into high (n = 74) and low (n = 86) NT-proBNP groups. The high NT-proBNP group had a lower weaning rate than the low NT-proBNP group [adjusted OR, 0.36 (0.170-0.756); P = 0.007]. We additionally found other predictors of weaning, such as sex, serum creatinine, urine output, and the score from the Acute Physiology and Chronic Health Evaluation, but all of these were not better than NT-proBNP in the predictability of weaning outcome. Neutrophil gelatinase-associated lipocalin, a well-known biomarker of acute kidney injury and originating from kidney, was not related with the CRRT weaning, which indicated the usefulness of NT-proBNP in the cases of CRRT despite originating from heart. The present study addresses the potential of NT-proBNP as an independent predictor of weaning from CRRT.

Predictors of Relapse in Adult-Onset Nephrotic Minimal Change Disease.

Minimal change disease (MCD) is a well-known benign primary glomerulonephritis because of its distinct rare tendency to progress to end-stage renal disease. However, factors associated with relapse in adults are not well known. We aimed to identify predictors of relapse in adult-onset MCD patients.A retrospective cohort of 195 patients with adult-onset primary MCD with nephritic syndrome and disease onset between 1979 and 2013 was followed up for >12 months. The number of relapses was counted and predictors of relapse were analyzed.A total of 195 patients were included. Median age at diagnosis was 38 years (IQR, 23-53 years) and 113 (57.9%) were men. During 81 months (IQR, 44-153 months) of follow-up, 92% of patients achieved remission after initial treatment. However, only 60 (32.8%) did not experience a relapse and 11 patients failed to remit. Among the remaining 124 patients, 65 experienced a relapse once or twice and 59 experienced a relapse more than twice. Younger onset age, increased severity of nephrotic features such as lower serum albumin levels and higher cholesterol level were associated with relapse. Interestingly, the grade of mesangial proliferation was lower in patients who experienced a relapse. Initial combined treatment with corticosteroids (CS) and cyclophosphamide reduced the number of relapses. In addition, patients with shorter treatment duration tended to experience relapse more often. Multivariate analysis showed that younger onset age, combined mesangial proliferation, initial treatment regimen, and treatment duration were independent risk factors for relapse. Progression to end-stage renal disease was developed in only a patient.In conclusion, more than two-thirds of adult-onset nephrotic MCD patients experienced relapse, although their renal progression was rare. Younger onset age, CS without cyclophosphamide treatment, and shorter treatment duration were independent risk factors for relapse in adult-onset MCD patients.

Low-dose paclitaxel ameliorates renal fibrosis by suppressing transforming growth factor-ß1-induced plasminogen activator inhibitor-1 signaling.

AIM: To investigate the effect of microtubule stabilization with low-dose paclitaxel on renal fibrosis, focusing on the transforming growth factor-ß1 (TGF-ß1)-induced plasminogen activator inhibitor-1 (PAI-1) signaling cascade. METHODS: Forty-eight rats were randomly assigned to four groups: sham/vehicle, sham/paclitaxel, unilateral ureteral obstruction (UUO)/vehicle and UUO/paclitaxel. Rats were treated with a 0.3 mg/kg intraperitoneal dose of paclitaxel or vehicle twice per week for 14 days. Half of the rats in each group were sacrificed respectively on day 7 and 14 after operation. Inner medullar collecting duct (IMCD) cells stimulated with TGF-ß1 were incubated with 0, 1 and 2 nM paclitaxel for 24 and 72 hours. Histological changes were assessed using periodic acid-Schiff and Masson's trichrome. The TGF-ß1-induced PAI-1 signaling and status of extracellular matrix proteins were evaluated by western blot analysis. RESULTS: In the UUO kidneys, paclitaxel significantly attenuated tubular damage and interstitial collagen deposition, as well as α-smooth muscle actin (α-SMA), TGF-ß1 and PAI-1 protein expression. Paclitaxel also inhibited the UUO-induced activation of Smad2/3 and c-Jun N-terminal kinase (JNK). However, paclitaxel treatment did not inhibit extracellular signal-regulated kinase 1/2 (ERK1/2) or p38 expression. In TGF-ß1-treated IMCD cells, treatment with 1 and 2 nM paclitaxel for 72 h reduced fibronectin, α-SMA and PAI-1 protein expression. Moreover, a 2 nM dose of paclitaxel for 24 h significantly inhibited the TGF-ß1-stimulated activation of Smad2/3, JNK and ERK1/2 in IMCD cells. CONCLUSION: Paclitaxel at low non-cytotoxic doses ameliorates renal fibrosis by inhibiting multiple steps in the TGF-ß1-induced PAI-1 signaling including Smads and mitogen-activated protein kinases.

Dysnatremia, its correction, and mortality in patients undergoing continuous renal replacement therapy: a prospective observational study.

BACKGROUND: Although dysnatremia has been reported to be correlated with mortality risk, this issue remains unresolved in patients undergoing continuous renal replacement therapy (CRRT). Furthermore, it has not been determined whether change in or correction of sodium is related to mortality risk in this subset. METHODS: A total of 569 patients were prospectively enrolled at the start of CRRT between May 2010 and September 2013. The patients were divided into 5 groups: normonatremia (135-145 mmol/L), mild hyponatremia (131.1-134.9 mmol/L), moderate to severe hyponatremia (115.4-131.0 mmol/L), mild hypernatremia (145.1-148.4 mmol/L), and moderate to severe hypernatremia (148.5-166.0 mmol/L). The non-linear relationship between sodium and mortality was initially explored. Subsequently, the odds ratios (ORs) for 30-day mortality were calculated after adjustment of multiple covariates. RESULTS: The relationship between baseline sodium and mortality was U-shaped. The mild hyponatremia, moderate to severe hyponatremia, and moderate to severe hypernatremia groups had greater ORs for mortality (1.65, 1.91, and 2.32, respectively) than the normonatremia group (all P values < 0.05). However, later sodium levels (24 and 72 h after CRRT) did not predict 30-day mortality. Furthermore, the changes in sodium over 24 or 72 h, including the appropriate correction of dysnatremia, did not show any relationships with mortality, irrespective of baseline sodium level. CONCLUSIONS: Sodium level at the start of CRRT was a strong predictor of mortality. However, changes in sodium level and the degree of sodium correction were not associated with the mortality risk in the patients with CRRT.

Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome.

Gitelman's syndrome (GS) is caused by loss-of-function mutations in SLC12A3 and characterized by hypokalemic metabolic alkalosis, hypocalciuria, and hypomagnesemia. Long-term prognosis and the role of gene diagnosis in GS are still unclear. To investigate genotype-phenotype correlation in GS and Gitelman-like syndrome, we enrolled 34 patients who showed hypokalemic metabolic alkalosis without secondary causes. Mutation analysis of SLC12A3 and CLCNKB was performed. Thirty-one patients had mutations in SLC12A3, 5 patients in CLCNKB, and 2 patients in both genes. There was no significant difference between male and female in clinical manifestations at the time of presentation, except for early onset of symptoms in males and more profound hypokalemia in females. We identified 10 novel mutations in SLC12A3 and 4 in CLCNKB. Compared with those with CLCNKB mutations, patients with SLC12A3 mutations were characterized by more consistent hypocalciuria and hypomagnesemia. Patients with 2 mutant SLC12A3 alleles, compared with those with 1 mutant allele, did not have more severe clinical and laboratory findings except for lower plasma magnesium concentrations. Male and female patients did not differ in their requirement for electrolyte replacements. Two patients with concomitant SLC12A3 and CLCNKB mutations had early-onset severe symptoms and showed different response to treatment. Hypocalciuria and hypomagnesemia are useful markers in differentiation of GS and classical Bartter's syndrome. Gender, genotypes or the number of SLC12A3 mutant alleles cannot predict the severity of disease or response to treatment.

Effects of sodium citrate on salt sensitivity and kidney injury in chronic renal failure.

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Alkali therapy attenuates the progression of kidney injury via Na/H exchanger inhibition in 5/6 nephrectomized rats.

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

Renal adverse effects of sunitinib and its clinical significance: a single-center experience in Korea.

BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. METHODS: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. RESULTS: One hundred and fifty-five patients (mean age, 58.7 ± 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. CONCLUSIONS: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.

Renal replacement therapy in Korea, 2012.

The Korean Society of Nephrology (KSN) launched the official end-stage renal disease (ESRD) patient registry in 1985, and an Internet online registry program was opened in 2001 and revised in 2013. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The status of renal replacement therapy in Korea at the end of 2012 is described in the following. The total number of ESRD patients was 70,211 at the end of 2012, which included 48,531 hemodialysis (HD) patients, 7,552 peritoneal dialysis (PD) patients, and 14,128 functioning kidney transplant (KT) patients. The prevalence of ESRD was 1,353.3 patients per million population (PMP), and the distribution of renal replacement therapy among ESRD patients was as follows: HD, 69.1%; PD, 10.8%; and KT, 20.2%. The number of new ESRD patients in 2012 was 11,742 (HD, 8,811; PD, 923; and KT, 1,738; the incidence rate was 221.1 PMP). The primary causes of ESRD were diabetic nephropathy (50.6%), hypertensive nephrosclerosis (18.5%), and chronic glomerulonephritis (18.1%). The mean urea reduction ratio was 67.9% in male and 74.1% in female HD patients. The mean Kt/V was 1.382 in male and 1.652 in female HD patients. The 5-year survival rates of male and female dialysis patients were 70.6% and 73.5%, respectively.

Gitelman's syndrome with vomiting manifested by severe metabolic alkalosis and progressive renal insufficiency.

Gitelman's syndrome is an autosomal recessive salt-losing tubulopathy showing hypokalemic hypomagnesemic hypocalciuria with metabolic alkalosis and hyperreninemic hyperaldosteronism. This syndrome is caused by mutations in the SLC12A3 gene that encodes sodium-chloride cotransporter expressed at the apical membrane of renal distal convoluted tubule. Symptoms and renal outcomes of Gitelman's syndrome are, in general, mild and benign, and renal insufficiency from Gitelman's syndrome associated with long-standing hypokalemia and volume depletion is extremely rare. Herein, we report a 27-year-old male patient with Gitelman's syndrome who manifested renal failure, hypokalemia, severe metabolic alkalosis and altered mentality. About one year ago, the patient had been transferred to Seoul National University Hospital, because of unsolved hypokalemia, and was diagnosed as Gitelman's syndrome by clinical features and genetic analysis of the SLC12A3 gene. The patient carries a missense mutation at one allele of SLC12A3 gene (c.781C>T, p.Arg261Cys). His mother is also heterozygous for the same mutation and she had a history of hypokalemia. On this admission, the patient had recurrent bouts of vomiting induced by psychiatric eating disorder and showed severe volume depletion with hypotension, azotemia and metabolic alkalosis. Intense hydration therapy and emergency hemodialysis transiently improved his fluid-electrolyte imbalance and renal function. However, renal dysfunction progressively deteriorated despite the medical treatment. Our findings suggest that even in Gitelman's syndrome, constant monitoring for volume status and other comorbid conditions should be employed to prevent progressive renal injury.