Autosomal dominant polycystic kidney disease in Colombia.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) that requires dialysis. Knowing geographical clusters can be critical for early diagnosis, progression control, and genetic counseling. The objective was to establish the prevalence, geographic location, and ethnic groups of patients with ADPKD who underwent dialysis or kidney transplant in Colombia between 2015 and 2019. METHODS: We did a cross-sectional study with data from the National Registry of Chronic Kidney Disease (NRCKD) managed by the High-Cost Diseases Fund (Cuenta de Alto Costo [CAC] in Spanish) between July 1, 2015, and June 30, 2019. We included Colombian population with CKD with or without renal replacement therapy (RRT) due to ADPKD. Crude and adjusted prevalence rates were estimated by state and city. RESULTS: 3,339 patients with ADPKD were included, period prevalence was 9.81 per 100,000 population; there were 4.35 cases of RRT per 100,000 population, mean age of 52.58 years (± 13.21), and 52.78% women. Seventy-six patients were Afro-Colombians, six were indigenous, and one Roma people. A total of 46.07% began scheduled dialysis. The highest adjusted prevalence rate was in Valle del Cauca (6.55 cases per 100,000 population), followed by Risaralda, and La Guajira. Regarding cities, Cali had the highest prevalence rate (9.38 cases per 100,000 population), followed by Pasto, Medellin, and Bucaramanga. CONCLUSIONS: ADPKD prevalence is lower compared to Europe and US; some states with higher prevalence could be objective to genetic prevalence study.

Prevalence of autosomal dominant polycystic kidney disease in Persian and Persian-related cats in Brazil.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease in cats. However, scarce data on its prevalence are available in Brazil. Persian cats and Persian-related breeds were assessed by molecular genotyping for a C to A transversion in exon 29 of PKD1 gene to determine ADPKD prevalence in a Brazilian population. Genomic DNA extracted from peripheral whole blood or oral swabs samples was used to amplify exon 29 of PKD1 gene employing a PCR-RFLP methodology. From a total of 616 animals, 27/537 Persian and 1/17 Himalayan cats showed the single-nucleotide variant (C to A) at position 3284 in exon 29 of feline PKD1. This pathogenic variation has been identified only in heterozygous state. The prevalence of ADPKD in Persian cats and Persian-related breeds was 5.03% and 1.6%, respectively. There was no significant association between feline breed, gender or age with ADPKD prevalence. Of note, the observed ADPKD prevalence in Persian cats and Persian-related breeds in Brazil was lower than the ones reported in other parts of the world. This finding may be related to genetic counseling and consequent selection of ADPKD-free cats for reproduction.

Prevalence of autosomal dominant polycystic kidney disease in Persian and Persian-related cats in Brazil / Prevalência da doença renal policística autossômica dominante em gatos Persas e raças relacionadas no Brasil

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease in cats. However, scarce data on its prevalence are available in Brazil. Persian cats and Persian-related breeds were assessed by molecular genotyping for a C to A transversion in exon 29 of PKD1 gene to determine ADPKD prevalence in a Brazilian population. Genomic DNA extracted from peripheral whole blood or oral swabs samples was used to amplify exon 29 of PKD1 gene employing a PCR-RFLP methodology. From a total of 616 animals, 27/537 Persian and 1/17 Himalayan cats showed the single-nucleotide variant (C to A) at position 3284 in exon 29 of feline PKD1. This pathogenic variation has been identified only in heterozygous state. The prevalence of ADPKD in Persian cats and Persian-related breeds was 5.03% and 1.6%, respectively. There was no significant association between feline breed, gender or age with ADPKD prevalence. Of note, the observed ADPKD prevalence in Persian cats and Persian-related breeds in Brazil was lower than the ones reported in other parts of the world. This finding may be related to genetic counseling and consequent selection of ADPKD-free cats for reproduction.

A doença renal policística autossômica dominante (DRPAD) é a doença genética mais comum em gatos. No entanto, poucos dados sobre sua prevalência estão disponíveis no Brasil. Gatos Persas e de raças relacionadas foram avaliados por genotipagem molecular para a transversão C→A no exon 29 do gene PKD1 felino para determinar a prevalência de DRPAD. DNA genômico extraído de sangue total periférico ou amostras de swabs orais foram utilizados para amplificar o exon 29 do gene PKD1 pela técnica de PCR-RFLP. De um total de 616 gatos, 27/537 Persas e 1/17 Himalaia mostraram a variante de nucleotídeo único (C→A) na posição 3284 no exon 29 do gene PKD1. Esta variante patogênica foi identificada apenas em heterozigose. A prevalência de DRPAD em gatos Persas e raças relacionadas foram de 5,03% e 1,6%, respectivamente. Não houve associações significativas entre raça, gênero ou idade dos felinos e incidência de DRPAD. A prevalência de DRPAD em gatos Persas e raças relacionadas no Brasil foi menor do que em outras partes do mundo, o que pode estar relacionado ao aconselhamento genético e consequente seleção de gatos sem ADPKD para reprodução.

Touchdown polymerase chain reaction detection of polycystic kidney disease and laboratory findings in different cat populations.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited genetic disease of cats, predominantly affecting Persian and Persian-related cats. A point mutation (C→A transversion) in exon 29 of the PKD1 gene causes ADPKD, and is the specific molecular target for genetic diagnosis in cats. The current study describes a newly developed touchdown polymerase chain reaction (PCR) to detect this single point mutation, using 2 primers specific for the mutant allele, adapted from an existing multiplex amplification refractory mutation system (ARMS PCR). Furthermore, correlations between the clinical outcomes of tested animals and the results of the genetic test were investigated. A total of 334 cats were tested, 188 from the Veterinary Hospital of Small Animals at the University of Brasilia, and 146 from an anti-rabies vaccine campaign of the Federal District. A total prevalence of 9% was evident among the samples, with 33% of the Persian cats testing positive, and 7% of the Brazilian long- and shorthaired cats testing positive. Prevalence was not correlated with gender or hemogram. Positive animals exhibited hyperglobulinemia ( P = 0.02). This research demonstrated that the mutation does not only occur in Persian and Persian-related cats, and that a touchdown PCR can be used to diagnose ADPKD.

[Autosomal dominant polycystic kidney disease in hemodialysis patients in Southern Brazil]. / Doenca renal policistica autossomica dominante em pacientes em hemodialise no sul do Brasil.

INTRODUCTION: Autosomal dominant polycystic kidney disease is the most common hereditary renal disease in humans. OBJECTIVE: To examine the prevalence, clinical and laboratory characteristics of patients with polycystic kidneys and relate disease manifestations by gender. METHODS: This was an observational and retrospective study. All the medical records of patients with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the coverage area of the 15th regional health Paraná (Brazil), were analyzed. RESULTS: The study included 48 patients with polycystic kidneys, the primary cause of stage 5 CKD. Disease prevalence was one in 10,912 people. The average age of dialysis initiation was 50.7 years and the follow-up time on dialysis until transplantation (36.5 months) was lower among men. Hypertension was the most frequent diagnosis in 73% of patients, predominantly in women (51.4%). The liver cyst was the most frequent extrarenal manifestations in men (60.0%). The death occurred in 10.4% of patients using hemodialysis, and 60% of men. The class of antihypertensive drug used was that acts on the renin-angiotensin system with higher frequency of use among women (53.3%). The post-dialysis urea was significantly higher in men. CONCLUSION: The prevalence of the disease is low among hemodialysis patients in southern Brazil. The differences observed between genders, with the exception of the post-dialysis urea, were not significant. The findings are different from those reported in North America and Europe.

Doenca renal policistica autossomica dominante em pacientes em hemodialise no sul do Brasil / Autosomal dominant polycystic kidney disease in hemodialysis patients in southern Brazil

Introdução: A doença renal policística autossômica dominante é a enfermidade renal hereditária mais comum em seres humanos. Objetivo: Analisar a prevalência, características clínicas e laboratoriais de pacientes com rins policísticos e relacionar as manifestações da doença por gênero. Métodos: Trata-se de um estudo observacional e retrospectivo. Foram revisados todos os prontuários médicos de pacientes com rins policísticos admitidos para hemodiálise entre 1995 e 2012, em quatro centros que atendem a área de abrangência da 15ª regional de saúde do Paraná, Brasil. Resultados: Fizeram parte do estudo 48 pacientes com rins policísticos, causa primária da doença renal crônica (DRC) estágio 5. A prevalência da doença foi de um em 10.912 habitantes. A média de idade de ingresso na hemodiálise (50,7 anos) e o tempo de seguimento em hemodiálise até o transplante (36,5 meses) foi menor nos homens. A hipertensão arterial foi o diagnóstico mais frequente em 73% dos pacientes, com predominância em mulheres (51,4%). O cisto hepático foi a manifestação extrarrenal mais frequente nos homens (60,0%). Foram a óbito 10,4% dos pacientes que faziam uso de hemodiálise, sendo 60% de homens. A classe de droga anti-hipertensiva mais utilizada foi a que atua no sistema renina-angiotensina, com maior frequência de uso nas mulheres (53,3%). A ureia pós-diálise foi significativamente maior em homens. Conclusão: A prevalência da doença é baixa entre pacientes em hemodiálise no sul do Brasil. As diferenças observadas entre os gêneros, com exceção da ureia pós, não foram significantes. Os dados encontrados são diferentes dos reportados na América do Norte e Europa. .

Introduction: Autosomal dominant polycystic kidney disease is the most common hereditary renal disease in humans. Objective: To examine the prevalence, clinical and laboratory characteristics of patients with polycystic kidneys and relate disease manifestations by gender. Methods: This was an observational and retrospective study. All the medical records of patients with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the coverage area of the 15th regional health Paraná (Brazil), were analyzed. Results: The study included 48 patients with polycystic kidneys, the primary cause of stage 5 CKD. Disease prevalence was one in 10,912 people. The average age of dialysis initiation was 50.7 years and the follow-up time on dialysis until transplantation (36.5 months) was lower among men. Hypertension was the most frequent diagnosis in 73% of patients, predominantly in women (51.4%). The liver cyst was the most frequent extrarenal manifestations in men (60.0%). The death occurred in 10.4% of patients using hemodialysis, and 60% of men. The class of antihypertensive drug used was that acts on the renin-angiotensin system with higher frequency of use among women (53.3%). The post-dialysis urea was significantly higher in men. Conclusion: The prevalence of the disease is low among hemodialysis patients in southern Brazil. The differences observed between genders, with the exception of the post-dialysis urea, were not significant. The findings are different from those reported in North America and Europe. .

Polycystic liver disease: a clinical review.

Polycystic liver disease rarely occurs in isolation as part of autosomal dominant polycystic liver disease, but more commonly, it exists as an extra-renal manifestation of autosomal dominant polycystic kidney disease. The pathogenesis of polycystic liver disease involves defects in the primary cilium of the cholangiocyte, with genetic mutations that impair key proteins integral to the complex functioning of cilia. While most patients are asymptomatic and require no intervention aside from reassurance and genetic counseling, in a minority of patients, polycystic liver disease creates a myriad of symptoms from the compressive effects of enlarged cysts, and can even cause malnutrition and liver decompensation in the severest of cases. In patients with symptomatic disease, a variety of interventional radiology or surgical techniques can be considered, including aspiration with sclerotherapy of a dominant cyst, fenestration, segmental hepatic resection, and even liver transplantation. Although there are no curative medical options for polycystic liver disease, somatostatin analogs hold promise and have shown minimal efficacy in human studies. However, further research is needed to develop more efficacious medical treatments.

[Co-inheritance of autosomal dominant polycystic kidney disease and sickle cell trait in African Americans]. / Co-herencia de poliquistosis renal autosómica dominante y hemoglobina con rasgo falciforme en afroamericanos.

BACKGROUND: Macroscopic haematuria secondary to renal cyst rupture is a frequent complication in autosomal dominant polycystic kidney disease (ADPKD). Sickle-cell disease is an autosomal recessive haemoglobinopathy that involves a qualitative anomaly of haemoglobin due to substitution of valine for the glutamic acid in the sixth position of 3-globin gene on the short arm of chromosome 11. For the full disease to be manifested, this mutation must be present on both inherited alleles. The severity of the disease is proportional to the quantity of haemoglobin S (Hb S) in the red cells; sickle-cell trait (Hb S <50%) and homozygous sickle-cell disease (Hb S >75%). In sickle-cell disease, the abnormal Hb S loses its rheological characteristics and is responsible of the various systemic manifestations including those of the kidney, such as macroscopic haematuria secondary to papilar necrosis. Despite the generally benign nature of the sickle-cell trait, several potentially serious complications have been described. Metabolic or environmental changes such as hypoxia, acidosis, dehydration, hyperosmolality or hyperthermia may transform silent sickle-cell trait into a syndrome resembling sickle-cell disease with vaso-occlusive crisis due to an accumulation of low deformable red blood cells in the microcirculation originating haematuria from papilar necrosis. On the other hand, it has been demonstrated an earlier onset of end-stage renal disease (ESRD), in blacks with ADPKD and sickle-cell trait when compared with blacks with ADPKD without the trait. PATIENTS AND METHODS: We studied 2 african-american families (4 patients) which presented with both ADPKD and sickle-cell trait (Hb S <50%). The diagnosis of sickle-cell trait was confirmed by haemoglobin electrophoresis. The renal volume was measured by magnetic resonance imaging (MRI). RESULTS: The proband subject in family 1 presented frequent haematuria episodes, associated to increase of renal volume, developed very early ESRD and was dialyzed at the age of 39 years. The other 3 patients in family 2 presented different degree of renal function. CONCLUSIONS: The presence of sickle haemoglobin should be determined in african-american and west-african patients with ADPKD because it is an important prognostic factor. Coherence of sickle-cell trait may have influence on ADPKD evolution to ESRD and other complications, such as cystic haemorrhages. MRI can identify intracystic haemorrhage and permit renal volume measure.

Frequency and clinical profile of patients with polycystic kidney disease in southern Brazil.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic nephropathies, affecting one in every 800-1000 individuals in the worldwide general population and 5-10% of hemodialysis patients. Little data concerning the prevalence of ADPKD in Brazil are available. Thus, the aim of the present study was to investigate both the frequency and clinical profile of ADPKD among hemodialysis patients in south of Brazil. METHODS: This cross-sectional study consisted of patients from 24 hemodialysis centers. Patients were screened for ADPKD by clinical, laboratorial, and image examination in medical records. RESULTS: Of 1326 patients on hemodialysis in the south of Brazil that composed this study, 99 (7.5%) had polycystic kidney as primary cause for chronic renal failure. Comparisons between ADPKD and non-ADPKD patients revealed no differences regarding mean age, gender, and ethnicity. CONCLUSIONS: Our data revealed that ADPKD is prevalent among patients on hemodialysis in the south of Brazil. In addition, the clinical profile of ADPKD is similar to reported data from North America and Europe, putatively due to the similar ethnic composition mainly based on European descents.