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One-third of patients with cirrhosis present kidney failure (AKI and CKD). It has multifactorial causes and a harmful effect on morbidity and mortality before and after liver transplantation. Kidney function does not improve in all patients after liver transplantation, and liver transplant recipients are at a high risk of developing chronic kidney disease. The causes of renal dysfunction can be divided into three groups: pre-operative, perioperative and post-operative factors. To date, there is no consensus on the modality to evaluate the risk of chronic kidney disease after liver transplantation, or for its prevention. In this narrative review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease in order to establish a risk categorization for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this context, and highlight the indications of combined liver–kidney transplantation.

Although living kidney donation is not a high-risk surgery, there is still a need to identify situations at risk of kidney disease after uninephrectomy. Estrogens exhibit a protective role against various nephropathies. The aim of this study was to assess renal adaptation following nephrectomy according to menopausal status in women. A prospective bicentric study including living women donors measured glomerular filtration rate (GFR) (inulin or 51−Cr-EDTA clearances) and kidney volume (using CT-scan and 3-dimensional reconstruction), before and after 1-year post-uninephrectomy. Renal adaptation was compared according to menopausal status. Sixteen non-menopausal women and 18 menopausal women were included. One year following uninephrectomy, the mean decrease in GFR (global population) was − 32 ± 12 ml/min/1.73 m2, and the mean increase in remnant kidney volume was + 32 ± 13 cm3/1.73 m2. No significant difference was observed between the two groups for both the decrease in GFR (-32.9 ± 13.3 in non-menopausal vs − 31.5 ± 9.9 in menopausal, ml/min/1.73 m2, p = 0.84), and the increase in kidney volume (+ 36.1 ± 13.4 in non-menopausal vs + 28.1 ± 12.5 in menopausal, cm3/1.73 m2, p = 0.09). Menopausal status did not influence kidney adaptation following uninephrectomy, and in this respect is not a potential limiting factor for living kidney donation.

Contains fulltext : 248375.pdf (Publisher’s version ) (Closed access) BACKGROUND: Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. Gitelman syndrome is caused by biallelic pathogenic variants in SLC12A3, encoding the Na(+)-Cl(-) cotransporter (NCC) expressed in the distal convoluted tubule. Pathogenic variants of CLCNKB, HNF1B, FXYD2, or KCNJ10 may result in the same renal phenotype of Gitelman syndrome, as they can lead to reduced NCC activity. For approximately 10 percent of patients with a Gitelman syndrome phenotype, the genotype is unknown. METHODS: We identified mitochondrial DNA (mtDNA) variants in three families with Gitelman-like electrolyte abnormalities, then investigated 156 families for variants in MT-TI and MT-TF, which encode the transfer RNAs for phenylalanine and isoleucine. Mitochondrial respiratory chain function was assessed in patient fibroblasts. Mitochondrial dysfunction was induced in NCC-expressing HEK293 cells to assess the effect on thiazide-sensitive (22)Na(+) transport. RESULTS: Genetic investigations revealed four mtDNA variants in 13 families: m.591C>T (n=7), m.616T>C (n=1), m.643A>G (n=1) (all in MT-TF), and m.4291T>C (n=4, in MT-TI). Variants were near homoplasmic in affected individuals. All variants were classified as pathogenic, except for m.643A>G, which was classified as a variant of uncertain significance. Importantly, affected members of six families with an MT-TF variant additionally suffered from progressive chronic kidney disease. Dysfunction of oxidative phosphorylation complex IV and reduced maximal mitochondrial respiratory capacity were found in patient fibroblasts. In vitro pharmacological inhibition of complex IV, mimicking the effect of the mtDNA variants, inhibited NCC phosphorylation and NCC-mediated sodium uptake. CONCLUSION: Pathogenic mtDNA variants in MT-TF and MT-TI can cause a Gitelman-like syndrome. Genetic investigation of mtDNA should be considered in patients with unexplained Gitelman syndrome-like tubulopathies.

International audience; Rationale & objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).Study design: Prospective longitudinal cohort study.Setting & participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.Predictor: Fasting urinary osmolality measured using delta cryoscopy.Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance.Analytical approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.Limitations: Fasting was self-reported.Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.

Metabolic acidosis is an early and deleterious complication of chronic kidney disease. Because it is frequently eubicarbonatemic, diagnosis may be difficult. In this issue, Gianella et al. suggest that lower urinary citrate excretion, considered as an homeostatic response to metabolic acidosis, may be helpful for early diagnosis and monitoring of alkali treatment. This study should be an incentive for further assessment of the tubular handling of urinary citrate in CKD patients and determination of the performance of urinary citrate for the diagnosis of eubicarbonatemic metabolic acidosis and monitoring of alkali therapy.

Our aim was to investigate the validity of osmolality from 24-h urine collection in examining the risk for calcium-oxalate (CaOx) kidney stone formation in patients with recurrent urolithiasis. Three hundred and twelve subjects (males/females: 184/128) from France with a history of recurrent kidney stones from confirmed or putative CaOx origin were retrospectively included in the study (46 ± 14 years, BMI: 25.3 ± 5.0 kg·m−2). Tiselius’ crystallization risk index (CRI) was calculated based on urinary calcium, oxalate, citrate, magnesium, and volume from 24-h samples. The diagnostic ability of 24-h urine osmolality to classify patients as high risk for kidney stone crystallization was examined through the receivers operating characteristics analysis. High risk for CaOx crystallization was defined as CRI > 1.61 and > 1.18, for males and females, respectively. The accuracy of urine osmolality to diagnose risk of CaOx stone formation (AUC, area under the curve) for females was 84.6%, with cut-off point of 501 mmol·kg−1 (sensitivity: 83.3%, specificity: 76.0%). Males had AUC of 85.8% with threshold of 577 mmo·kg−1 (sensitivity: 85.5%, specificity: 77.6%). A negative association was found between 24-h urine volume and osmolality (r = − 0.63, P 501 and > 577 mmol·kg−1, in female and in male, respectively, was associated with a risk for CaOx kidney stone formation in patients with a history of recurrent urolithiasis. Thus, when CaOx origin is confirmed or suspected, 24-h urine osmolality provides a simple way to define individualized target of urine dilution to prevent urine crystallization and stone formation.

Resume Introduction Estimer le statut volemique du patient est indispensable au diagnostic de certains desordres hydroelectrolytiques, telles que les hyponatremies et dyskaliemies. Les parametres biocliniques classiquement utilises dans ce but ne sont toutefois pas suffisamment discriminants dans les situations chroniques moderees. L’objectif de ce travail etait de determiner les parametres biologiques les mieux correles au statut volemique. Methodes Le statut volemique a ete determine par la mesure du volume extracellulaire en utilisant le volume apparent de distribution de l’inuline chez des patients non œdemateux, n’ayant pas d’insuffisance cardiaque ou hepatique. Les patients ont ete repartis en trois groupes selon le volume extracellulaire: hypovolemiques, normovolemiques et hypervolemiques. Les donnees cliniques ainsi que differents parametres biologiques mesures ont ete compares entre les trois groupes et correles au volume extracellulaire. Resultats Les donnees de 91 explorations ont ete colligees. Il n’y avait pas de difference entre les trois groupes concernant les parametres cliniques, la protidemie et la natriurese. Les parametres biologiques les mieux correles au volume extracellulaire etaient le rapport calciurie/creatininurie a jeun (r = 0,51; p Conclusion En plus de l’acide urique, deja propose comme marqueur biologique pour estimer le statut volemique, la calciurie a jeun et le pH urinaire a jeun pourraient aussi etre utilises.

Background Gitelman syndrome is a salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter. Previous studies suggested an intermediate phenotype for heterozygous carriers. Methods To evaluate the phenotype of heterozygous carriers of pathogenic SLC12A3 mutations, we performed a cross-sectional study of patients with Gitelman syndrome, heterozygous carriers, and healthy noncarriers. Participants measured their BP at home for three consecutive days before hospital admission for blood and urine sampling and an oral glucose tolerance test. Results We enrolled 242 participants, aged 18-75 years, including 81 heterozygous carriers, 82 healthy noncarriers, and 79 patients with Gitelman syndrome. The three groups had similar age, sex ratio, and body mass index. Compared with healthy noncarriers, heterozygous carriers showed significantly higher serum calcium concentration (P=0.01) and a trend for higher plasma aldosterone (P=0.06), but measures of home BP, plasma and urine electrolytes, renin, parathyroid hormone, vitamin D, and response to oral glucose tolerance testing were similar. Patients with Gitelman syndrome had lower systolic BP and higher heart rate than noncarriers and heterozygote carriers; they also had significantly higher fasting serum glucose concentration, higher levels of markers of insulin resistance, and a three-fold higher sensitivity to overweight. According to oral glucose tolerance testing, approximately 14% of patients with Gitelman syndrome were prediabetic, compared with 5% of heterozygous carriers and 4% of healthy noncarriers. Conclusions Heterozygous carriers had a weak intermediate phenotype, between that of healthy noncarriers and patients with Gitelman syndrome. Moreover, the latter are at risk for development of type 2 diabetes, indicating the heightened importance of body weight control in these patients.

Acid retention occurs early during the course of chronic kidney disease (CKD). Studies conducted in patients with CKD suggest that alkali supplementation may slow CKD progression. However, the diagnosis of acid retention is challenging when plasma bicarbonate concentration is still normal. In this issue, Goraya et al. suggest that urinary citrate may predict acid retention in eubicarbonatemic patients with stages 1 and 2 CKD . Although interesting, this claim yet requires confirmation by further studies.

In a control population, we filed the 24-hour urinary calcium to set normal values, based on weight, BMI and menopause. By assessing calcium intake, 25OHD, PTH, CTX, GFR, we wanted to study how these could influence calcium excretion. A total of 317 subjects of 55.82 ± 12.6 years were studied: 249 women (210 were postmenopausal) and 66 men. Mean urinary calcium 24h was 4.07 ± 2.53 mmol: 3.99 ± 2.89 in men, 3.54 ± 2.44 in premenopausal women, 4.18 ± 2.42 in postmenopausal women. 24-hour urine calcium was lower in overweight subjects whether they are men or women. It was positively correlated to 25OHD, CTX, GFR, serum calcium and negatively to PTH, BMI and weight. In conclusion, urinary calcium was lower in overweight subjects, it increases after menopause. Dietary calcium intake seems little involved in explaining variations in urinary calcium which depends essentially on bone remodeling (CTX), GFR, levels of vitamin D and PTH.

Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO 2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1–4. All patients had measured glomerular filtration rate (mGFR) by 51 Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m 2 . Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06–3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98–3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO 2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.

Resume Introduction L’insuffisance en vitamine D peut-elle etre predite par l’interrogatoire ? Induit-elle une hyperparathyroidie secondaire potentiellement vectrice d’hyperresorption osseuse ? Cela chez des sujets non osteoporotiques de la cinquantaine chez qui cette hormone est frequemment dosee. Methodes Des patients hospitalises pour arthrose ou consultant pour bilan de menopause, non insuffisants renaux, non traites par vitamine D ont rempli un questionnaire sur l’ensoleillement et ont eu des dosages de calcemie, creatininemie, 25OH vitamine D, PTH et CTX serique. Resultats Cinq cent vingt-six sujets âges de 54,6 ans (71 % de femmes) ont ete explores tout au long des 12 mois de l’annee. La concentration de 25OH vitamine D etait correlee au score d’ensoleillement et variait selon les mois de l’annee, contrairement aux valeurs de PTH et de CTX. De novembre a mai, plus de 90 % de sujets avaient des concentrations de 25OH vitamine D 65 pg/mL associee a une augmentation des CTX. Conclusion L’insuffisance en vitamine D peut etre predite par l’interrogatoire et induit tres rarement une hyperparathyroidie secondaire.

Patients with Gitelman syndrome (GS), an inherited salt-losing tubulopathy, are usually treated with potassium-sparing diuretics or nonsteroidal anti-inflammatory drugs and oral potassium and magnesium supplementations. However, evidence supporting these treatment options is limited to case series studies. We designed an open-label, randomized, crossover study with blind end point evaluation to compare the efficacy and safety of 6-week treatments with one time daily 75 mg slow-release indomethacin, 150 mg eplerenone, or 20 mg amiloride added to constant potassium and magnesium supplementation in 30 patients with GS (individual participation: 48 weeks). Baseline plasma potassium concentration was 2.8±0.4 mmol/L and increased by 0.38 mmol/L (95% confidence interval [95% CI], 0.23 to 0.53; P

Inactivation of the B1 proton pump subunit (ATP6V1B1) in intercalated cells (ICs) leads to type I distal renal tubular acidosis (dRTA), a disease associated with salt- and potassium-losing nephropathy. Here we show that mice deficient in ATP6V1B1 (Atp6v1b1-/- mice) displayed renal loss of NaCl, K+, and water, causing hypovolemia, hypokalemia, and polyuria. We demonstrated that NaCl loss originated from the cortical collecting duct, where activity of both the epithelial sodium channel (ENaC) and the pendrin/Na(+)-driven chloride/bicarbonate exchanger (pendrin/NDCBE) transport system was impaired. ENaC was appropriately increased in the medullary collecting duct, suggesting a localized inhibition in the cortex. We detected high urinary prostaglandin E2 (PGE2) and ATP levels in Atp6v1b1-/- mice. Inhibition of PGE2 synthesis in vivo restored ENaC protein levels specifically in the cortex. It also normalized protein levels of the large conductance calcium-activated potassium channel and the water channel aquaporin 2, and improved polyuria and hypokalemia in mutant mice. Furthermore, pharmacological inactivation of the proton pump in β-ICs induced release of PGE2 through activation of calcium-coupled purinergic receptors. In the present study, we identified ATP-triggered PGE2 paracrine signaling originating from β-ICs as a mechanism in the development of the hydroelectrolytic imbalance associated with dRTA. Our data indicate that in addition to principal cells, ICs are also critical in maintaining sodium balance and, hence, normal vascular volume and blood pressure.

Murine unilateral ureteral obstruction (UUO), a major model of progressive kidney disease, causes loss of proximal tubular mass and formation of atubular glomeruli. Adult C57BL/6 mice underwent a sham operation or reversible UUO under anesthesia. In group 1, kidneys were harvested after 7 days. In group 2, the obstruction was released after 7 days, and a physiological study of both kidneys was performed 30 days later. Renal blood flow (RBF), glomerular filtration rate (GFR), urine protein, and albumin excretion were measured after ligation of either the left or right ureter. Glomerular volume (periodic acid-Schiff), glomerulotubular integrity and proximal tubular mass ( Lotus tetragonolobus lectin), and interstitial collagen (Sirius red) were measured by histomorphometry. Obstructed kidney weight was reduced by 15% at 7 days but was not different from sham after a 30-day recovery. Glomerular volume and proximal tubular area of the obstructed kidney were reduced by 55% at 7 days, but normalized after 30 days. Interstitial collagen deposition increased 2.4-fold after 7 days of UUO and normalized after release. However, GFR and RBF were reduced by 40% and urine albumin/protein ratio was increased 2.8-fold 30 days after release of UUO. This was associated with a 50% reduction in glomerulotubular integrity despite a 30-day recovery ( P < 0.05 for all data). We conclude that release of 7-day UUO can arrest progression but does not restore normal function of the postobstructed kidney. Although the remaining intact nephrons have hypertrophied, glomerular injury is revealed by albuminuria. These results suggest that glomerulotubular injury should become the primary target of slowing progressive kidney disease.

Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 25 avril 2016

Objective: Hyperkalemia can occur following unilateral adrenalectomy for primary aldosteronism due to hypoaldosteronism. We hereby report the cases of 4 male patients exhibiting prolonged failure of the renin-aldosterone (RA) axis in association with normal-to-high kalemia or labile blood pressure and, most significantly, a decrease in extracellular fluid volume (ECFV).Methods: Prior to surgery, all patients exhibited hypokalemic hypertension, with documented primary aldosteronism. Within a few weeks of undergoing unilateral adrenalectomy, the patients developed either mild hyperkalemia or labile blood pressure. Complementary investigations revealed a decrease in measured ECFV with inappropriate normal renal sodium excretion, low supine plasma renin activity, and insufficient orthostatic-related aldosterone production. The adrenocorticotropic hormone (ACTH) stimulation test demonstrated no glucocorticoid deficiency, along with responsive aldosterone secretion.Results: The discrepancy between the aldosterone response in the orthostatic position versus the ACTH stimulation test suggested that the aldosterone deficiency was largely due to RA axis depression. Recovery was confirmed between 3 and 18 months in all but one patient, the latter still requiring mineralocorticoid substitution 23 months later.Conclusion: Following unilateral adrenalectomy for primary aldosteronism, the occurrence of mild hyperkalemia prompted a functional evaluation of the RA system using an orthostatic stimulation test, rather than simply measuring baseline values and evaluating the glucocorticoid axis. In such cases, where RA depression is confirmed to cause latent hypovolemia, all treatments likely to further decrease plasma volume should be avoided, while mineralocorticoid substitution may be required.Abbreviations: ACTH = adrenocorticotropic hormone; AVS = adrenal vein sampling; BP = blood pressure; CT = computed tomography; ECFV = extracellular fluid volume; PA = primary aldosteronism; RA = renin-aldosterone

Gitelman’s syndrome is an autosomal recessive salt losing nephropathy caused by inactivated mutations of the SLC12A3 gene, encoding the NaCl cotransporter of the distal convoluted tubule. We report a French family with five affected members over two generations suggesting a dominant transmission. After SLC12A3 sequencing of seven individuals, four mutations were detected. Pseudo-dominant transmission was explained by the union of a compound heterozygous woman (two mutations on one allele and one mutation on the other) with a heterozygous healthy man. This study shows the importance of complete genetic analysis of families with unusual presentation.

Recent studies indicate that pendrin, an apical Cl-/HCO3- exchanger, mediates chloride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involved in extracellular fluid volume regulation. The purpose of this study was to test whether pendrin is regulated in vivo primarily by factors that are associated with changes in renal chloride transport, by aldosterone, or by the combination of both determinants. For achievement of this goal, pendrin protein abundance was studied by semiquantitative immunoblotting in different mouse models with altered aldosterone secretion or tubular chloride transport, including NaCl loading, hydrochlorothiazide administration, NaCl co-transporter knockout mice, and mice with Liddle's mutation. The parallel regulation of the aldosterone-regulated epithelial sodium channel (ENaC) was examined as a control for biologic effects of aldosterone. Major changes in pendrin protein expression were found in experimental models that are associated with altered renal chloride transport, whereas no significant changes were detected in pendrin protein abundance in models with altered aldosterone secretion. Moreover, in response to hydrochlorothiazide administration, pendrin was downregulated despite a marked secondary hyperaldosteronism. In contrast, alpha-ENaC was markedly upregulated, and the molecular weight of a large fraction of gamma-ENaC subunits was shifted from 85 to 70 kD, consistent with previous results from rat models with elevated plasma aldosterone levels. These results suggest that factors that are associated with changes in distal chloride delivery govern pendrin expression in the connecting tubule and cortical collecting duct.

Patients with degenerative dementia often show language disorders, but little is known about their verbal (VC) and non-verbal communication (NVC). Our aim was to analyse VC and NVC in patients with standard criteria of mild-moderately severe dementia (MMSE ≥14/30) resulting from Alzheimer's disease (AD; 29 cases), behavioural variant of frontotemporal dementia (FTD; 16), or dementia with Lewy bodies (DLB; 13). We used the Lille Communication Test, which addresses three domains: participation in communication (PC: greeting, attention, participation), VC (verbal comprehension, speech outflow, intelligibility, word production, syntax, verbal pragmatics and verbal feedback), and NVC (understanding gestures, affective expressivity, producing gestures, pragmatics and feedback). Patients were compared with 47 matching control subjects. AD patients were partially impaired (p≤0.01) in PC (greeting), and more definitely in VC, especially by verbal comprehension and word finding difficulties and to a much lesser degree in verbal pragmatics (responding to open questions, presenting new information), while NVC was mostly preserved. FTD patients were severely impaired in PC. VC difficulties were related to lexical-semantic, syntactic and more specifically pragmatic problems. NVC was impaired by difficulties in affective expressivity, pragmatics and feedback management. DLB patients showed modest difficulties with VC. PC, VC and NVC strongly correlated with performance in the dementia rating scale. In conclusion, the profile of communication difficulties was quite different between groups. FTD patients showed most severe difficulties in PC and verbal and non-verbal pragmatics, in relation to their frontal lesions. AD patients had prominent impairment of lexical-semantic operations.

Udgivelsesdato: 2009-Jul PURPOSE OF REVIEW: Abnormal renal sodium handling plays a pivotal role in the pathophysiology of arterial hypertension. Though sodium is present in the diet as a chloride salt, most studies have focused on the renal mechanisms of sodium transport and their regulation, and very few have investigated the impact of chloride. However, strong evidence indicates that chloride may play a very important role in the 'prohypertensive' effects of sodium. RECENT FINDINGS: Several observations indicate that sodium has to be administered as NaCl and not as NaHCO3 to raise arterial blood pressure. Recently, genetic studies have pointed out the critical role of the most distal parts of the nephron in regulating sodium balance and blood pressure. Interestingly, in those segments, the transport of Na+ and Cl- proceeds separately, through different molecules. Recent evidence has demonstrated that an apical Cl-/HCO3- exchanger called pendrin is an absolute requirement for chloride reabsorption in the collecting system, indicating that chloride absorption is not passive and paracellular but is mediated by the intercalated cells. Importantly, pendrin disruption protects mice against mineralocorticoid-induced hypertension and impairs renal adaptation to a low NaCl diet. Moreover, recent findings suggest several mechanisms by which chloride transport might affect NaCl balance and blood pressure. SUMMARY: Pendrin-mediated chloride transport through intercalated cells appears to be an independent and important determinant of renal NaCl handling and therefore might represent a new target for blood pressure control.