Is Chronic Kidney Disease a Critical Health Problem in Madeira Island?

Chronic kidney disease (CKD) is an ever-growing global public health problem affecting more than 10% of the general population worldwide. CKD is associated with an increased risk of cardiovascular disease and all-cause mortality, representing a major burden to the healthcare system. Although multiple studies have determined CKD prevalence in different countries, there is still a significant knowledge gap between epidemiological surveys and real data recorded by healthcare providers. Regarding the Portuguese population, most recent studies revealed a CKD prevalence of 20.9%. However, there is an irregular distribution of CKD prevalence in the country. For example, considering the Madeiran population, a non-published review of lab results of nearly 130,000 patients in our database allowed us an estimation of 20%. Thus, to better comprehend CKD prevalence and its characterization in this region, we designed a study comprising previous studies' strengths as well as aiming to overcome their limitations. The principal objective is to calculate global CKD prevalence in Madeira Island and stratify it by stage of CKD, allowing comparison of our results with recent literature on this subject. We intend to contribute with relevant epidemiological data in the characterization of CKD prevalence in Portugal and, simultaneously, have a more active role in CKD prevention and allocation of resources.

Fabry Disease p.M290I Mutation is Related to Organ Involvement: A Case Report.

Fabry disease (FD) is an X-linked hereditary disease. It results from mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A (α-Gal A) and progressive accumulation of undegraded glycosphingolipids in cell lysosomes. Enzyme replacement therapy (ERT) can improve the natural course of this disease, but an early diagnosis is crucial for a successful treatment. We describe the case of a female diagnosed with chronic proteinuric kidney disease in the postpartum period. Despite receiving optimal medical treatment, the disease progressed and she started renal replacement therapy (RRT) with peritoneal dialysis (PD). Five years later, she was enrolled in a pilot screening study for FD, and the heterozygous mutation c.870G>C (p.Met290Ile; M290I) in exon six of the GLA gene was found. The family screening revealed the presence of this mutation in the patient's father and daughter. The proband did not meet the criteria for a definitive FD diagnosis, but she remained under follow-up at our nephrology metabolic diseases consultation, as the mutation was described as pathogenic and associated with a classic FD phenotype. Later that same year, reassessment exams revealed a worsening left ventricle mass index (LVMi), a new ischemic cerebral lesion, and a substantial increase in serum globotriaosylsphingosine (LysoGb3) levels. These clinical changes led to a decision to initiate ERT. p.M290I is a previously known but poorly described GLA mutation. To our knowledge, this is the first report of p.M290I mutation-associated disease activity that offers strong evidence of its pathogenicity.

Celiac Disease as a Rare Cause of Membranous Nephropathy: A Case Report.

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. A non-negligible number of cases are associated with systemic conditions. We report a case of a 50-year-old man who presented with nephrotic syndrome six months after being diagnosed with celiac disease. Although the patient showed disappearance of circulating immunoglobulin A (IgA) anti-tissue transglutaminase antibodies following a gluten-free diet, he had a sudden onset of nephrotic syndrome presenting with severe hypoalbuminemia. Other secondary causes were promptly excluded leading to the assumption of celiac disease-associated membranous nephropathy with remission after treatment with angiotensin system blockade and a gluten-free diet. The goal of this case report is to alert the clinic towards this rare association aiming for an early diagnosis and adequate selection of long-term therapy.

Lower donated kidney volume is associated with increased risk of lower graft function and acute rejection at 1 year after living donor kidney-a retrospective study.

Kidney volume has been proven to be a surrogate marker of nephron mass and renal function. We studied 190 donor and recipient pairs undergoing living donor kidney transplantation at our institution during 9 years. Different metrics of donor kidney volume (DKV) were explored: alone or indexed to recipient's anthropometry, as body surface area (BSA). DKV/BSA (min. 49.7; P33rd 77.7; P67th 95.3; max. 176 cm3 /m2 ) was chosen given its higher correlation with eGFR at 1 year, and recipients were divided according to its tertiles (T). The eGFR at 1 year was lower in T1, when compared with T2 (P = 0.015) and T3 (P < 0.001). In a multivariable model, a regression spline revealed that a DKV/BSA lower than 80 was significantly associated with an eGFR at 1 year <60. In the first 6 years, the overall annual eGFR slope was -0.90 ml/min/year. Acute rejection occurred in 19%, 11%, and 0% of patients in T1, T2, and T3, respectively (P < 0.001). DKV/BSA increased stepwise from cellular- (n = 12) to antibody-mediated (n = 7) AR cases and to those without AR (n = 171; P = 0.002; no AR versus cellular AR). Lower DKV/BSA ratio was associated with significantly worse graft function and higher incidence of AR. Hence, it can be a tool for better selection of donors in order to improve graft outcomes, particularly in the setting of multiple potential living donors or kidney paired exchange programs.

Remaining kidney volume indexed to weight as a strong predictor of estimated glomerular filtration rate at 1 year and mid-term renal function after living-donor nephrectomy - a retrospective observational study.

The donors' estimated glomerular filtration rate (eGFR) after living nephrectomy has been a concern, particularly in donors with smaller kindeys. Therefore, we developed this retrospective observational study in 195 donors to determine the ability remaining kidney volume indexed to weight (RKV/W) to predict eGFR at 1 year through multivariate linear regression and to explore this relationship between annual eGFR change from 1 to 4 years postdonation evaluated by a linear mixed model. Comparing RKV/W tertiles (T1, T2, T3), RKV/W was a good predictor of 1-year eGFR which was significantly better in T3 donors. Gender, predonation eGFR, and RKV/W were independent predictors of eGFR at 1-year. In a subgroup with predonation eGFR < 90mL/min/1.73 m2 , a significant prediction of eGFR < 60mL/min/1.73 m2 was detected in males with RKV/W ≤ 2.51cm3 /kg. Annual eGFR (ml/min/year) change from 1 to 4 years was + 0.77. RKV/W divided by tertiles (T1-T3) was the only significant predictor: T2 and T3 donors had an annual eGFR improvement opposing to T1. RKV/W was a good predictor of eGFR at 1 year, independently from predonation eGFR. A higher RKV/W was associated with improved eGFR at 1 year. A decline in eGFR on the four years after surgery was only noticeable in donors with RKV/W ≤ 2.13cm3 /kg.

Impact of Pancreatic Autoantibodies in Pancreas Graft Survival After Pancreas-Kidney Transplantation.

BACKGROUND: In simultaneous pancreas-kidney transplantation (SPKT), persistence or recurrence of pancreatic autoantibodies (PAs) has been associated with pancreas graft (PG) autoimmune-driven injury. Our aim was to analyze the impact of PAs on PG survival. METHODS: Between January 1, 2000, and December 31, 2017, we studied 139 patients with post-SPKT anti-glutamic acid decarboxylase (GAD) autoantibody. Alloimmune (ALI) events were defined as PG rejection and/or de novo donor-specific antibodies (DSA). Hence, 3 groups were defined: patients without ALI events or anti-GAD (n = 42), those with ALI events (n = 14), or those only with autoimmune events (positive for anti-GAD and no ALI events; n = 83). RESULTS: Male sex was predominant (n = 72, 52%). Median age was 35 years (interquartile range: 31-39) and median follow-up was 6-7 years (interquartile range: 4.1-9.2). Regarding anti-GAD positivity post-SPKT (n = 90, 65%), no differences were observed concerning age, sex, anti-HLA antibodies, HLA mismatch number and de novo DSA. ALI events were present in 10% (n = 14). PG survival 15 years post-SPKT was better in patients without immune events (96%) followed by those with ALI (69%) and autoimmune events (63%) (P = .025). Anti-GAD was associated to higher annualized mean Hb1AC (P = .006) and lower mean C-peptide (P = .013). According to pre- and post-SPKT anti-GAD status, conversion from negative to positive was associated to worse (63%) 10-year PG survival (P = .044), compared to persistence of negative (100%) or positive anti-GAD (88%). Anti-islet cell and anti-insulin autoantibodies had no impact. CONCLUSION: Anti-GAD presence post-SPKT was associated to higher pancreas disfunction and lower PG survival. De novo anti-GAD seems to offer a particular risk of PG failure.

Obstructive Acute Kidney Injury with Maintenance of Diuresis: A Case of Ureter Bifidity / Lesión Renal Aguda Obstructiva con Mantenimiento de la Diuresis: Un Caso de BifidezUreteral

Abstract Percutaneous kidney biopsyin transplanted kidneys remains an essential and commonly performed procedure required for diagnostic and prognostic information. Hemorrhage is the main complication of renal graft biopsy. We report a case of a 47-year-old caucasian womanadmitted to perform an ultrasound(US)-guided biopsy of the renal graft. Six hours later, she presented with macroscopic hematuriawhichimproved after urethral catheterization and intravenous hydration. However the hematuria reappeared associated with anemia and worsening of the serum creatinine value. The US study, revealed hydronephrosis with high Doppler derived renal resistive index compatible with clot obstruction.Despite the vesical lavage with drainage of several clots, the patient rapidly progressed to hemorrhagic shock with worsening of renal function. Pelvic computed tomography (CT) revealed calyx and pelvis duplicity and ureter bifidity which merged into a single ureter and inserted into the right anterolateral wall of the bladder. The inferior ureter was enlarged due to an obstructive clot. Most acute obstructive uropathies are associated with significant pain or the abrupt diminution of urine flow. The presence of ureter bifidity in the CT study explained the maintenance of significantdiuresis despite obstruction, located only to the lower ureter but with sufficient functional impact to condition acute kidney injury (AKI).

Resumen La biopsia renal percutánea en riñones trasplantados sigue siendo un procedimiento esencial y común, necesario para obtener información diagnóstica y pronóstica. La hemorragia es la principal complicación de la biopsia de injerto renal. Presentamos un caso de una mujer caucásica de 47 años, quien fue hospitalizada para la realización de una biopsia de injerto renal guiada por ultrasonido (US). Seis horas después, presentó hematuria macroscópica que mejoró después de la cateterización uretral e hidratación intravenosa. Sin embargo, la hematuria reapareció asociada con anemia y empeoramiento del valor sérico de creatinina. El estudio de US reveló, mediante Doppler, una hidronefrosis con alto índice de resistencia renal, compatible con obstrucción por un coágulo. A pesar del lavado vesical con drenaje de varios coágulos, la paciente progresó rápidamente a choque hemorrágico con empeoramiento de la función renal. La tomografía computarizada (TC) pélvica reveló la duplicidad del cáliz y la pelvis y la bifidez ureteral, que se fusionó en un solo uréter y se insertó en la pared anterolateral derecha de la vejiga. El uréter inferior se agrandó debido a un coágulo obstructivo. La mayoría de las uropatías obstructivas agudas están asociadas con dolor significativo o la disminución abrupta del flujo de orina. La presencia de la bifidez del uréter en el estudio de TC explicó el mantenimiento de una diuresis significativa a pesar de la obstrucción, localizada solo en el uréter inferior, pero con suficiente impacto funcional como para provocar insuficiencia renal aguda (IRA).