FC 012PRIMARY KIDNEY DISEASE IMPACTS OUTCOME IN CKD PREGNANCIES: COMPLICATIONS IN COL4A3-5 RELATED DISEASE (ALPORT SYNDROME) VS OTHER CKD PREGNANCIES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Rozemarijn Snoek ◽  
Margriet Gosselink ◽  
Liffert Vogt ◽  
Margriet De Jong ◽  
Agne Cerkauskaite ◽  
...  

Abstract Background and Aims Chronic kidney disease (CKD) affects approximately 3% of pregnant women. CKD increases the risk of pregnancy complications such as prematurity, low birthweight and pre-eclampsia. Also, kidney function can deteriorate more quickly due to pregnancy. There is limited knowledge on pregnancy outcomes in specific kidney diseases. The aim of the ALPART network is to study pregnancy outcomes differentiated by CKD aetiology. We have started with COLA3-5 related disease (Alport syndrome), which is one of the most prevalent monogenic kidney diseases. Comparing outcomes in COLA3-5 related disease to pregnancies with other CKD aetiologies allows us to investigate whether this specific diagnosis impacts outcome in CKD pregnancies. Method The ALPART network is an international 15-center network, which aims to include ∼200 COLA3-5 related disease pregnancies. In this intermediary analysis, we present data on 109 pregnancies from 68 women with COLA3-5 related disease. We compared outcomes to a cohort of 457 CKD stage 1-2 patients (a similar CKD stage as our cohort) of diverse aetiology from a 2015 Italian study and 159,924 women from the general Dutch population. Results The main pregnancy and kidney outcomes are presented in Figure 1. Foetal outcomes were better in COLA3-5 pregnancies than in pregnancies of women with CKD stage 1-2 of diverse aetiology. We saw less prematurity (17% vs 36% respectively) and a higher mean birthweight of 3216 ± 663 gram compared to 2768 ± 680 in the Italian cohort. Maternal kidney outcomes should be interpreted with caution (>30% missing data): proteinuria (73%) and hypertension (30%) were more frequent in COLA3-5 pregnancies than the Italian cohort. In the ALPART cohort, 10% developed severe hypertension. Median eGFR was not impacted by pregnancy and decline of eGFR before and after pregnancy were not significantly different between groups. Conclusion Fetal outcomes in pregnancies with COLA3-5 related disease seem to be more favorable than in a cohort with mixed cause of CKD. In this intermediary analysis, proteinuria levels and frequency of new-onset hypertension in pregnancy are higher. There is no significant eGFR loss during pregnancy or increased eGFR deterioration in the long-term. The differences between COLA3-5 and general CKD pregnancies underscore the importance of investigating pregnancy outcomes in specific kidney disease phenotypes to ensure adequate (pre-) pregnancy counselling and care.

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-Hui Shi ◽  
Mu-Jin Ye ◽  
Song-Chang Chen ◽  
Jun-Yu Zhang ◽  
Yi-Yao Chen ◽  
...  

BackgroundAlport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in COL4A5 at Xq22 accounts for 80–85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling.MethodsPrenatal diagnoses were performed by amplifying targeted regions of COL4A5. Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase.ResultsPrenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (<3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes.ConclusionThe PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Landler ◽  
S Bro ◽  
B Feldt-Rasmussen ◽  
D Hansen ◽  
A.L Kamper ◽  
...  

Abstract Background The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population. Purpose To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD. Method Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines. Results 63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese. Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls. Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group. Conclusion In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD. Figure 1. Estimated GFR vs. GLS & histogram of GLS Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark


Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 15
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Harika Alpay ◽  
Assiya Kanatbayeva ◽  
Aigul Balmukhanova

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2–18 years with CKD stages 1–5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5–1.8) pmol/L versus 0.65 (0.22–1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
María del Mar Del Águila García ◽  
Antonio M Poyatos Andújar ◽  
Ana Isabel Morales García ◽  
Margarita Martínez Atienza ◽  
Susana García Linares ◽  
...  

Abstract Background and Aims Hereditary renal disease (HRD) is still underdiagnosed: although we know aspects related to autosomal dominant polycystic kidney disease (ADPKD), we know little about the incidence and prevalence of other entities such as Alport syndrome. Altogether, HRD can represent 15% of individuals undergoing renal replacement therapy (RRT) or could even be higher. The advancement of genetics at the healthcare level let to achieve accurate and early renal diagnoses, as well as the incorporation of genetic counseling to families, all of which will result in better management of the disease in its initial stages and the possibility of offering reproductive options that avoid transmission to offspring. Our objective is to know the performance offered by the implementation of the ERH panel through Next Generation Sequencing (NGS) in our healthcare area. Method Observational-descriptive study of 259 probands (141 men / 118 women), mean age of 46 years (30 pediatric / 123 over 50 years), with chronic kidney disease and suspected hereditary cause attended in the specialized consultation of our centers from October 2018 to October 2020. The DNA extracted from leukocytes obtained by venipuncture was processed with Nephropathies Solution version 3 panel (SOPHiA Genetics) according to the manufacturer's protocol. This panel covers the coding regions and splicing junctions of 44 HRD-related genes such as nephrotic syndromes, polycystic kidney diseases, Bartter syndromes, Alport syndrome, CAKUT or tubulopathies (table 1). The sequencing of the libraries was done in a MiSeq (Illumina Inc), the bioinformatic analysis of the data and annotation of variants was performed using the SOPHiA DDM 5.8.0.3 software, and the revision of variants by consulting the main databases (ClinVar, Exac, HGMD, NCBI, PKD Foundation, LOVD). Results The panel was informative (pathogenic or probably pathogenic) in 80/259 patients (31%) and 56/259 cases (21.66%) of variants of uncertain significance (VSI) were detected. Autosomal dominant polycystic kidney disease accounted for 76.2% of the variants identified (56.2% PKD1, 20% PKD2), following Alport syndrome with 15% and the alterations in the PKHD1 gene associated with renal polycystic disease in its recessive form with about 4% (Figure 1). We have also identified a case of autosomal dominant tubulointerstitial kidney disease associated with the UMOD gene that was not suspected until the genetic study was performed. We highlight that 45% (36/80) of the variants identified as responsible for the renal disease are not yet described. Overall, the most prevalent type of mutation is that which produces displacement in the reading frame or frameshift (Figure 2). Individually, frameshift is the most frequent alteration in PKD1, PKD2 and COL4A5, while for PKHD1, COL4A3 and COL4A4 it is missense. Conclusion Our NGS HRD panel a) offers an adequate diagnostic performance at the healthcare level, with definitive results in 1 out of 3 cases and has also allowed the performance of many carrier studies among family members b) is able of diagnosing the most frequent disease, ADPKD and Alport syndrome, as well as unresolved or poorly characterized cases, and c) opens the horizon for new diagnoses, all without increasing costs by outsourcing services. All this makes the genetic study of renal pathology a useful and efficient strategy. These results encourage us to enhance the resources in this area that we consider to be of strategic value.


2017 ◽  
Vol 98 (1) ◽  
pp. 5-9
Author(s):  
T L Nastausheva ◽  
O A Zhdanova ◽  
N S Nastausheva ◽  
L I Stahurlova ◽  
I V Grebennikova

Aim. To conduct comparative analysis of height, weight and body mass index in children with stages 1 to 3 of chronic kidney disease (CKD) caused by recurrent urinary tract infection due to congenital anomalies of kidney and urinary tract.Methods. The study was performed on 210 children: 110 patients examined in 2001-2002 (group 1) and 100 children examined in 2011-2012 (group 2). Stage 1 of CKD was observed in 94 (85.4%) children in group 1 and in 93 (93%) in group 2, stage 2 - in 16 (14.6%) and 7 (7%) patients, respectively. From both groups patients matched by sex, age, diagnosis and social status were selected: 20 patients with stage 1, 19 children with stage 2; in addition, 6 children with stage 3 were examined.Results. Nowadays children with CKD stage 1 are taller compared to patients of the beginning of the XXI century (Z-score: -0.14±1.43 and 0.20±0.98 respectively, p=0.01). Significant differences in weight were found in children with stage 1 in 2011-2012 compared to the patients in 2001-2002 (0.18±0.46 and 0.78±1.19 for groups 1 and 2, respectively, р=0.026). A tendency towards decrease of average height in children with stage 3 is observed compared to patients with stage 1, i.e. due to the progression of the disease.Conclusion. The data obtained reflect modern tendencies towards increase of children height and weight. No significant differences were found in physical development parameters of children with stages of chronic kidney disease 1 and 2 examined at the same time period but a tendency towards children’s height decrease from stages 1 to 3 of CKD of non-glomerular etiology was revealed.


2020 ◽  
Vol 10 (3) ◽  
Author(s):  
Flávia Silveira ◽  
Káthia Zuntini ◽  
Márcia Silveira ◽  
Lohanna Tavares ◽  
Juliana Mendes ◽  
...  

OBJECTIVES: This study aims to present the confirmed cases of SARS-CoV-2 infection in pediatric patients with chronic and acute kidney diseases admitted to a tertiary pediatric hospital. METHODS: Descriptive and retrospective observational study with all children hospitalized between March and June 2020 who had, simultaneously, SARS-CoV-2 infection and renal pathologies. Of this total of patients, those who had another underlying disease besides the renal disease were excluded. RESULTS: During the period, nine children with kidney disease were admitted to the hospital and had infection confirmed by the new coronavirus through positive RT-PCR. Regarding the underlying disease, seven had only kidney disease, three of whom had stage 5 chronic kidney disease; one, with stage 1 chronic kidney disease; one, with cortic-sensitive nephrotic syndrome; and two, with acute kidney injury. Two patients in this study had already undergone kidney transplantation, used immunosuppressants and had their doses reduced due to the infectious condition. Only one required oxygen therapy and transfer to the intensive care unit, but was not intubated and returned to the ward within 24 hours. CONCLUSIONS: According to the cases described, the pediatric population with kidney disease, including those using immunosuppressants due to acute transplant rejection, seems to evolve without severe COVID-19, therefore there is no great divergence in relation to the population of the same healthy age group.


2019 ◽  
Vol 21 (12) ◽  
pp. 1172-1180 ◽  
Author(s):  
Fernanda Chicharo Chacar ◽  
Marcia Mery Kogika ◽  
Andréa C Ferreira ◽  
Khadine K Kanayama ◽  
Archivaldo Reche

ObjectivesMagnesium has been ‘the forgotten ion’ for many years. Over the past decade, however, the role of magnesium in essential physiological functions and several illness conditions have been elucidated. Nevertheless, the investigation of magnesium in cats with chronic kidney disease (CKD) and nephrolithiasis is yet to be determined. The purpose of this study was to investigate whether CKD cats with nephrolithiasis have changes in total serum magnesium concentrations, and whether magnesium disorders may be associated with other electrolyte disturbances, as well as with prognosis. We also aimed to evaluate whether total serum magnesium concentration differs between CKD cats with and without nephrolithiasis.MethodsTotal serum magnesium concentrations were assessed in 42 cats with CKD with stage 1–4 nephrolithiasis. The correlation between magnesium and other electrolytes, as well as Kaplan–Meier survival analysis, were performed. We also selected 14 control cats with CKD without nephrolithiasis age-matched with 14 cats with CKD with nephrolithiasis.ResultsHypermagnesemia was observed in 16/42 (38.1%) and hypomagnesemia in 6/42 (14.3%) cats. Serum magnesium abnormalities were observed in cats of all stages, and marked hypermagnesemia was noted in cats with stage 4 CKD with nephrolithiasis ( P <0.001). There was a negative correlation between total serum magnesium and ionized calcium ( r = −0.64; P <0.01), and a positive correlation between total serum magnesium and serum phosphorus ( r = 0.58, P = 0.01). Cats with CKD with nephrolithiasis and hypomagnesemia or hypermagnesemia had higher mortality than those with normal total serum magnesium concentration ( P <0.01), regardless of CKD stage. There was no difference in total serum magnesium concentration between CKD cats with and without nephrolithiasis.Conclusions and relevanceCats with CKD with nephrolithiasis have magnesium abnormalities. Hypomagnesemia and hypermagnesemia were associated with an increase in mortality, and thus total serum magnesium abnormalities may be used as prognostic factors in these cases.


KYAMC Journal ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 43-47
Author(s):  
Md Moniruzzaman Khan ◽  
Zesmin Fauzia Dewan ◽  
AKM Shahidur Rahman ◽  
Bakhtiare Md Shoeb Nomany ◽  
Ahmed Salam Mir ◽  
...  

Background: Atorvastatin, a member of HMG CO-A reductase inhibitors, has been shown to have renoprotective effect in patients with Chronic Kidney Disease (CKD). Statins are supposed to decrease the oxidized lipid particles, suppress the activity of inflammatory mediators and prevent vascular thrombosis and thus could minimize renal cell damage. Losartan, an antihypertensive drug also diminishes proteinuria in patients with chronic kidney diseases or diabetes mellitus. Therefore the effect of concurrent use of atorvastatin and losartan on Glomerular Filtration Rate (GFR) could be a matter of interest from both Pharmacological and Clinical perspective. Objective: To assess the renoprotective effect of atorvastatin and losartan in patients with chronic kidney disease treated at Bangabandhu Sheikh Mujib Medical University (BSMMU). Materials and Method: Total forty four (44) patients suffering from CKD (stage one to stage three) were enrolled into two groups. Patients in Group A, received atorvastatin (10 mg) and losartan (50 mg) once daily for eight weeks. Patients in Group B, received losartan but not atorvastatin for the same duration. Serum creatinine level was measured at the commencement and also after eight weeks to calculate estimated glomerular filtration rate (eGFR) in individual patients with MDRD (Modification of Diet in Renal Disease) study equation. Results: There was significant (P < 0.001) reduction of Serum Creatinine and significant (P < 0.001) increase in e GFR in the patients, treated with atorvastatin and losartan. Conclusion: Concurrent administration of atorvastatin and losartan increased glomerular filtration rate (GFR) significantly in patients with chronic kidney disease. KYAMC Journal Vol. 10, No.-1, April 2019, Page 43-47


2016 ◽  
Vol 311 (1) ◽  
pp. F120-F130 ◽  
Author(s):  
George Jarad ◽  
Russell H. Knutsen ◽  
Robert P. Mecham ◽  
Jeffrey H. Miner

Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout ( Alb−/−) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb+/− mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout ( Col4a3−/−) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3−/−; Alb−/− mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3−/−; Alb+/+ and Col4a3−/−; Alb+/− mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy.


F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 186
Author(s):  
Daniel Landau ◽  
Ruth Schreiber ◽  
Anya Kleinman ◽  
Alina Vodonos ◽  
Hannah Shalev

Background: The incidence and prevalence of pediatric chronic kidney disease (p-CKD) in developed countries has previously been estimated to be 12 and 75 cases/106 population respectively, much lower than reports in young adults (age 20-40) (40,000/106). Thus, the extent of p-CKD may be underestimated.Methods: Being the only Pediatric Nephrology center in Southern Israel, we reviewed all detected cases of p-CKD (stages 1-5) between 1994-2008. We then prospectively summarized the incidence and prevalence of CKD between 2009-2010. Results: We retrospectively identified 192 children (53.9% of Bedouin origin, 53.4% males, median diagnosis age: 1 year) with CKD. The prevalence in December 2008 was 795 cases/106 for all CKD stages and 331/106 for CKD stage >2. Calculated incidence for the study period (1994-2008) was 46/106/year. The main CKD etiologies were: hypodysplasia: 35%; obstructive uropathy: 13%; genetic renal diseases: 28% and glomerulonephritis: 15%. The proportions of children in each CKD stage were as follows: stage 1: 50%; stages 2-4: 30%; stage 5: 20%. During a subsequent two-year study period we identified 26 new CKD cases (incidence: 54 cases/106/year). Conclusions: p-CKD rates in our area are higher than reported and maybe even higher if asymptomatic populations are screened. Fifty percent of detected cases have CKD stage 1. This may contribute significantly to CKD beyond the pediatric age.


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