scholarly journals Complications of Polycystic Kidney Disease and Relation With Disease Progression: An Observational Retrospective Study

2020 ◽  
Author(s):  
Mònica Pérez-Mir ◽  
Laura Carreras-Planella ◽  
Francesc Borràs ◽  
Josep Bonet ◽  
Maribel Troya
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Retrospective Study ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
High Blood Pressure ◽  
Inherited Disease ◽  
Polycystic Kidney ◽  
Renal Complication

Abstract Background: Autosomal dominant polycystic kidney disease (ADPKD) is a renal inherited disease characterized by the growth of bilateral renal cysts that lead to deterioration in renal function and end-stage renal disease (ESRD). These patients frequently present complications like urinary tract infection, acute pyelonephritis, acute or chronic pain, renal lithiasis or high blood pressure (HBP). The aim of this study is to compare the renal evolution in ADPKD patients with renal complications and/or HBP compared to those without complications nor HBP.Methods: Observational retrospective study of 29 ADPKD patients with normal renal function and <70 years followed up in our center. Clinical and analytical information of 2010, 2015 and 2017 were determined.Results: 29 patients were enrolled with a median age of 41 years [34-54], eighteen women (62,1%) and eleven men. Median of estimation of glomerular function rate (eGFR) was 85.8ml/min [70.7-115.6] in 2010, 76.0 ml/min [57.0-99.9] in 2015 and 63.1ml/min [45.0-95.8] in 2017. Eight patients (27.6%) have never had kidney complication nor HBP. Nine patients (31.0%) have normal blood pressure, 6 others (20.7%) have well controlled high blood pressure (HBP) and 14 (48.3%) have badly controlled HBP. When patients were divided between those who have never presented a complication (C-) and those who present renal complication and/or HBP (C+), the first group presented better kidney function. When patients were segregated into those who have never presented complication or well-controlled HBP (CHBP-) and those with renal complication and/or badly-controlled HBP (CHBP+) no differences were found at the initial eGFR, but a faster worsening of kidney function in CHBP+ group.Conclusions: In ADPKD patients, the decrease in eGFR is significantly important in individuals showing complications (including HBP) compared to those who did not present complications. Individuals with complications and badly-controlled HBP show even greater differences in kidney function decrease compared with patients without complications or well controlled HBP.

TOLVAPTAN USE IN SEVERE NEONATAL AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD): THE PHARMACEUTICAL CHALLENGE

2016 ◽  
Vol 101 (9) ◽  
pp. e2.58-e2 ◽  
Author(s):  
Kazeem Olalekan ◽  
Andy Fox ◽  
Rodney Gilbert
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Hospital Pharmacist ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor ◽  
Paediatric Formulation

BackgroundUnlicensed medications are used all the time in the management of diseases in childhood. Tolvaptan (Jinarc®) is a vasopressin V2-receptor antagonist licensed for use to slow the progression of cyst development and renal insufficiency of ADPKD in adults with CKD stage 1 to 3 with evidence of rapidly progressing disease. Studies of animal models implicate the antidiuretic hormone arginine vasopressin and its messenger cyclic adenosine monophosphate (cAMP) as promoters of kidney-cyst cell proliferation and luminal fluid secretion. The suppression of vasopressin release by means of high water intake, genetic elimination of vasopressin, and vasopressin V2-receptor blockade all reduce the cyst burden and protect kidney function1 A Phase 3 trial showed that Tolvaptan, as compared with placebo, slowed down the increase in total kidney volume and decline in kidney function in adults (average 39 yrs) with ADPKD over a 3-year period.2 ADPKD is the most common form of polycystic kidney disease (PKD) typically late in onset and results from mutation of either of two genes: PKD1 and PKD2. Autosomal recessive polycystic kidney (ARPKD), the other form of PKD, is 20 times less common, presents primarily in infancy and childhood, is typically more severe, and commonly associated with hypertension. ARPKD results from mutation of PKHD1. In spite of these differences, there is growing evidence to suggest that ADPKD and ARPKD are more related than previously suspected.3 Bilineal inheritance of PKD1 abnormalities has been reported to cause extremely severe disease resembling ARPKD.4 The use of Tolvaptan in the management of PKD in children is therefore expected to become more important.AimTo describe the first known UK use of Tolvaptan in a neonate with severe ADPKD and the role of the hospital pharmacist in facilitating the use.MethodThe role descriptor of hospital pharmacists produced by the World Health Organisation (WHO) was adapted and used to map the pharmaceutical challenges of using Tolvaptan in this child. The descriptor include: (i) Promotion of rational prescribing of drugs, (ii) Use of specialist pharmacists networks to gain greater expertise; (iii) Monitor compliance and therapeutic response and report adverse drug reactions; (iv) ensure supply of high quality products; (v) partake in planning and implementation of clinical trials.ResultsThe use of Tolvaptan for indication other than hyponatraemia and other endocrine uses are not routinely commissioned by NHS England. In view of the exceptionality of this case – a severe neonatal form of ADPKD with estimated prevalence of the order of 1 in tens of millions, an Individual Funding Request (IFR) application was made and was approved. The application was supported by financial information provided by the hospital pharmacist who facilitated the application process. Using available information and formulation knowledge, a suspension was eventually recommended and was well tolerated. This resulted in approximately 85% reduction in the cost of treatment over six months. Tolvaptan produced the expected aquaresis and blood pressure reduction. Initial dose of 0.1 mg/kg/day was used and increased according to weight and clinical response. Initial monitoring parameters, which included 4 hourly blood pressure, urine and electrolytes and hepatic function, were recommended. Electrolyte supplements were adjusted accordingly. At 2-month review point, there was no oedema of leg and face but the kidneys were still enlarged. The long term effect on cyst burden and kidney function is being evaluated and will feed into the IFR process.ConclusionThe use of unlicensed medications in children poses a number of pharmaceutical challenges and can be managed through a multidisciplinary approach to treatment intervention. It also re-enforce the paediatric formulation challenge to pharmaceutical companies in which formulation needs are prioritised and existing data are better used to facilitate paediatric formulation development.

scholarly journals Overexpression of TGF-β1 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease

2020 ◽  
Vol 319 (6) ◽  
pp. F1135-F1148
Author(s):  
Yan Zhang ◽  
Yuqiao Dai ◽  
Archana Raman ◽  
Emily Daniel ◽  
July Metcalf ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Combined Therapy ◽  
Polycystic Kidney ◽  
Tgf Β1 ◽  
Cyst Growth

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous fluid-filled cysts, extensive fibrosis, and the progressive decline in kidney function. Transforming growth factor-β1 (TGF-β1), an important mediator for renal fibrosis and chronic kidney disease, is overexpressed by cystic cells compared with normal kidney cells; however, its role in PKD pathogenesis remains undefined. To investigate the effect of TGF-β1 on cyst growth, fibrosis, and disease progression, we overexpressed active TGF-β1 specifically in collecting ducts (CDs) of phenotypic normal ( Pkd1RC/+) and Pkd1RC/RC mice. In normal mice, CD-specific TGF-β1 overexpression caused tubule dilations by 5 wk of age that were accompanied by increased levels of phosphorylated SMAD3, α-smooth muscle actin, vimentin, and periostin; however, it did not induce overt cyst formation by 20 wk. In Pkd1RC/RC mice, CD overexpression of TGF-β1 increased cyst epithelial cell proliferation. However, extensive fibrosis limited cyst enlargement and caused contraction of the kidneys, leading to a loss of renal function and a shortened lifespan of the mice. These data demonstrate that TGF-β1-induced fibrosis constrains cyst growth and kidney enlargement and accelerates the decline of renal function, supporting the hypothesis that a combined therapy that inhibits renal cyst growth and fibrosis will be required to effectively treat ADPKD.

scholarly journals Intracranial aneurysm as extra-renal manifestation of polycystic kidney disease: A case report

2018 ◽  
Vol 75 (5) ◽  
pp. 525-530
Author(s):  
Violeta Rabrenovic ◽  
Slobodan Culafic ◽  
Milorad Rabrenovic ◽  
Tamara Dragovic ◽  
Sasa Tresnjic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Renal Failure ◽  
Renal Function ◽  
Kidney Disease ◽  
Intracranial Aneurysm ◽  
Polycystic Kidney Disease ◽  
Stage Iv ◽  
Polycystic Kidney ◽  
Tract Infections

Introduction. Polycystic kidney disease is a hereditary kidney disease characterized by the occurrence of cysts (fluid-filled enlargements) in cortex or medula of the kidney, and is inherited in an autosomal dominant or autosomal recessive manner. In addition to multiple cysts in kidneys, there may be many extra-renal manifestations (cysts of the liver, pancreas, lungs, heart, etc.), among which the most serious one is intracranial aneurysms. Case report. A 57-year-old female patient with polycystic kidney disease and stage IV renal failure was hospitalized at our clinic due to decreased renal function, the development of urinary tract infections, headaches and unregulated blood pressure despite the usual treatment. This patient also had a number of associated diseases: obesity, diabetes mellitus (the insulindependent type), hypothyroidism, and depression syndrome. After better regulation of blood pressure, resolved urinary tract infections and improved renal function, there were still persistent headaches (resulting in the excessive use of analgesics). With adequate preparation, multislice computed tomography (MSCT) angiography of blood vessels of the head was performed. As a result, we diagnosed the saccular intracranial aneurysm (IA) with anterior localization. Regarding the symptoms, age and comorbidity, digital subtraction angiography (DSA) was performed, and showed saccular IA (5.2 mm ? 4 mm), with wide neck affecting both middle cerebral artery branches (MCA). During the procedure the stent was placed, which filled the aneurysm with spirals, cutting it off from circulation. After the successful procedure and without further complications, the patient no longer had headaches and blood pressure was maintained within the required limits with stable parameters of chronic renal failure. Conclusion. The case of the patient with polycystic kidney disease, stage IV chronic renal failure, with a number of comorbidities (headache, obesity, hypertension, diabetes mellitus, hypothyroidism) and diagnosed with symptomatic intracranial aneurysm was successfully solved with a multidisciplinary approach, emphasizing the importance of teamwork in daily practice.

Blood pressure and renal function in autosomal dominant polycystic kidney disease

1997 ◽  
Vol 11 (5) ◽  
pp. 592-596 ◽  
Author(s):  
Tomáš Seeman ◽  
Milan Sikut ◽  
Martin Konrad ◽  
Hana Vondřichová ◽  
Jan Janda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

P0234LOW URINARY CITRATE LEVELS ARE NOT SPECIFIC OF AUTOSOMAL POLYCYSTIC KIDNEY DISEASE (ADPKD) AND ARE PRESENT WHEN RENAL FUNCTION IS IMPAIRED IN ALL NEPHROPATIES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Francisco-Jose Borrego-Utiel ◽  
Enoc Merino Garcia ◽  
Isidoro Herrera ◽  
Clara Moriana Dominguez ◽  
Victoria Camacho Reina ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Polycystic Kidney Disease ◽  
Normal Renal Function ◽  
Serum Bicarbonate ◽  
Polycystic Kidney ◽  
Glomerular Diseases ◽  
Urinary Citrate

Abstract Background and Aims In polycystic kidney disease (PKD) it is frequently found a reduction in urinary citrate that is related with degree of renal impairment but it is unknown if this alteration is specific or if it is also present in other nephropathies. Recently it has been suggested that urinary citrate could be a marker of covert metabolic acidosis and reflects acid retention in chronic kidney disease (CKD). Our aim was to compare urinary citrate in PKD with other renal diseases and to show its relation with serum bicarbonate and excretion of uric acid and calcium. Method We determined citrate, calcium and uric acid in 24-hour urine in patients with PKD and with other nephropathies with varied degree of renal impairment followed in a outpatient clinic of nephrology. Results We included 291 patients, 119 with glomerular diseases, 116 with PKD, 21 with other nephropathies, and 35 patients with normal renal function. Urinary citrate was higher in women (Females 309±251 mg/gCr vs. males 181±145 mg/gCr, p&lt;0.001) and in patients with normal renal function (normal 380±210 mg/gCr; PKD 203±166 mg/gCr; glomerular 279±282 mg/gCr; p&lt;0,001). PKD patients showed similar values of urinary citrate to patients with glomerular diseases and with other nephropathies. We observed a progressive reduction in urinary citrate parallel to degree of renal impairment, in a comparable way among patients with PKD and glomerular diseases. We did not observe a relationship between urinary citrate and serum bicarbonate levels. Calcium and uric acid elimination in ADPKD patients was similar to other nephropathies and lower to patients with normal renal function. However, serum uric acid was significantly higher in glomerular patients than other nephropathies after adjust with glomerular filtration rate and sex. Conclusion Hypocitraturia is not specific of PKD but it is also present in all nephropathies. Urinary citrate are related to degree of renal impairment and it is not related with serum bicarbonate. We think that it could be interesting to study urinary citrate as a marker of renal function and its role as prognostic factor of renal deterioration.

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