Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Bartter syndrome; Parathyroid hormone; PhosphateSíndrome de Bartter; Hormona paratiroidea; FosfatoSíndrome de Bartter; Hormona paratiroïdal; FosfatBackground Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. Methods Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). Results A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs −0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate—standard deviation score < −2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. Conclusions Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.This project has been supported by the European Reference Network for Rare Kidney Diseases (ERKNet), which is partly co-funded by the European Union within the framework of the Third Health Programme ‘ERN-2016-Framework Partnership Agreement 2017–2021’. This work is generated within the European Society for Paediatric Nephrology working group on inherited renal disorders. This work was supported by an Innovation Grant 19OI06 from the Dutch Kidney Foundation (to T.N.)

Enteric Budesonide in Transplant and Native IgA Nephropathy: Real-World Clinical Practice

Budesonide; Transplant; NephropathyBudesonida; Trasplante; NefropatíaBudesonida; Trasplantament; Nefropati

Progression of Interstitial Fibrosis and Tubular Atrophy in Low Immunological Risk Renal Transplants Monitored by Sequential Surveillance Biopsies: The Influence of TAC Exposure and Metabolism

Coeficient de variació; Biòpsies de protocol; Trasplantament renalCoeficiente de variación; Biopsias de protocolo; Trasplante renalCoefficient of variation; Protocol biopsies; Renal transplantationThe combination of tacrolimus (TAC) and mycophenolate is the most widely employed maintenance immunosuppression in renal transplants. Different surrogates of tacrolimus exposure or metabolism such as tacrolimus trough levels (TAC-C0), coefficient of variation of tacrolimus (CV-TAC-C0), time in therapeutic range (TTR), and tacrolimus concentration dose ratio (C/D) have been associated with graft outcomes. We explore in a cohort of low immunological risk renal transplants (n = 85) treated with TAC, mycophenolate mofetil (MMF), and steroids and then monitored by paired surveillance biopsies the association between histological lesions and TAC-C0 at the time of biopsy as well as CV-TAC-C0, TTR, and C/D during follow up. Interstitial inflammation (i-Banff score ≥ 1) in the first surveillance biopsy was associated with TAC-C0 (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.50–0.96; p = 0.027). In the second surveillance biopsy, inflammation was associated with time below the therapeutic range (OR: 1.05 and 95% CI: 1.01–1.10; p = 0.023). Interstitial inflammation in scarred areas (i-IFTA score ≥ 1) was not associated with surrogates of TAC exposure/metabolism. Progression of interstitial fibrosis/tubular atrophy (IF/TA) was observed in 35 cases (41.2%). Multivariate regression logistic analysis showed that mean C/D (OR: 0.48; 95% CI: 0.25–0.92; p = 0.026) and IF/TA in the first biopsy (OR: 0.43, 95% CI: 0.24–0.77, p = 0.005) were associated with IF/TA progression between biopsies. A low C/D ratio is associated with IF/TA progression, suggesting that TAC nephrotoxicity may contribute to fibrosis progression in well immunosuppressed patients. Our data support that TAC exposure is associated with inflammation in healthy kidney areas but not in scarred tissue.The authors received grants from Red de Investigación Renal (REDinREN RD16/0009/0030), Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI 18/01704, PI 18/01382), the Spanish Society of Transplantation and a Diaverum Spain restricted grant. Betty Chamoun has been supported by a VHIR (Vall Hebron Institute Research) grant

Treatment and long-term outcome in primary nephrogenic diabetes insipidus

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. Conclusion: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems

Treatment and long-term outcome in primary nephrogenic diabetes insipidus.

Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome

Treatment and long-term outcome in primary nephrogenic diabetes insipidus

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. Conclusion: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems