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Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, responsible for 10% of patients on renal replacement therapy. The disease is well known to be associated with many extrarenal manifestations. Leukopenia may also be present, even if it is not commonly identified as a typical extrarenal manifestation. Herein we describe two case reports of ADPKD patients with leukopenia. The first case is about a 47-year-old patient affected by ADPKD, regularly treated with peritoneal dialysis, who showed a progressive reduction of white blood cell count, mostly of lymphocytes. Lymphocytic leukopenia was so severe that, when he was called for transplantation from a deceased donor, he was considered temporarily not eligible. We then describe a second ADPKD patient regularly treated with peritoneal dialysis, who had stable lymphopenia for years. Six years after starting PD, it was necessary to perform bone marrow aspirate to investigate the simultaneous presence of hypogammaglobulinemia together with M-protein and to exclude monoclonal gammopathy. All the exams performed did not show any significant results, the patients were re-included in the waiting list and one of them was transplanted. Given our experience and what is reported in the literature, there seems to be enough evidence to consider leukopenia as an extrarenal manifestation of ADPKD. However, the clinical significance of leukopenia in ADPKD patients is not known. It could be interesting to investigate the leucocytes' function and if ADPKD patients with leukopenia are more susceptible to infection, or not. Moreover, it would be very useful to analyze the relationship between such manifestation and genotype/phenotype., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and accounts for∼10% of patients on renal replacement therapy. In the last decade, no specific treatment was available and only preventive measures could be put in place to delay the onset of ESRD. Following the results of the TEMPO 3:4 study, tolvaptan was approved in many countries, for the purpose of slowing the progression of renal insufficiency. In Italy tolvaptan is available since 2016 for patients with chronic kidney disease (CKD) stage 1-3, and since 2020 for patients with CKD stage 4, who fulfil the criteria of "rapid disease progression", according to the European recommendations. After this approval, Italian nephrology units have had to change their organization to be able to identify the patients eligible for the drug and to guarantee frequent patient monitoring. In this paper, we present our three-year experiences with tolvaptan, focusing on its safety profile and tolerability, but also on the high burden of care that such therapy represents not only for doctors, but also for patients. Strategies to implement remote monitoring may be useful to reduce the burden of assistance on one side, and the medicalization of ADPKD patients in the early stage of the disease, on the other., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease with variable rate of progression. It is associated with inter- and intra-familial variability. Neutrophil gelatinase-associated lipocalin (NGAL) has been implicated in pathological conditions and it is proposed as a biomarker for CKD progression. Our aim was to evaluate whether NGAL could be a good marker for progression of ADPKD, as we hypothesized. ADPKD patients with confirmed mutations (PKD1 n=33; PKD2 n=17) were enrolled and followed in a prospective study. Creatinine (sCr) and NGAL values were measured at baseline and on follow-up. Plasma NGAL was measured by Triage point of care test. CKD progression was defined as 15% decrease in eGFR from baseline to follow-up. Patients were divided into 2 groups based on median baseline NGAL and compared by the Kaplan-Meier curve. We enrolled 50 ADPKD pts (60%M age 41 yrs); mean sCr 1.30.7 mg/dl and median eGFR was 62 mL/min/1.73 m2. NGAL values are inversely correlated with baseline eGFR (r=-0.64, p<0.001). There was weak correlation between baseline NGAL and subsequent change in eGFR (r=0.28, p=0.05). 9/50 of patients had NGAL below limits of detection (60 pg/ml); median NGAL level was 79 pg/ml. At follow-up, 12 patients (24%) had progression as defined. No statistically significant relationship between higher NGAL and ADPKD progression was observed. We did not observe a relationship between NGAL and CKD progression in ADPKD patients; however 18% of patients had undetectable plasma NGAL levels. This raises doubt about the utility of the current NGAL assay as a biomarker for CKD progression in this population.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) in adults. It is associated with both inter- and intra- familial variability, which can be explained by genetic heterogeneity, modifier genes and a genetic background. NGAL, a 25-kDa protein released from tubular cells after harmful stimuli, is a new biomarker. Recent studies suggest a possible role for NGAL in CKD. The aim of this study was to investigate NGAL in the context of genotype-phenotype correlation in ADPKD., Methods: We measured plasma NGAL, creatinine (Cr), and urea in 18 ADPKD patients on dialysis (PKD1&#95;TRS), 29 of their relatives with CKD stage II-III (PKD1&#95;AMB), 33 wild-type relatives (PKD1&#95;WT), 12 subjects in CKD stage II-III with confirmed mutation in PKD2 and 30 healthy controls (CTR). Cr, urea and CysC were measured according to standard methods. Plasma NGAL was measured using point-of-care test. Estimated glomerular filtration rate (eGFR) was calculated with a 4-variable standardized-MDRD formula., Results: Plasma NGAL, CysC, Cr and urea levels in PKD1&#95;TRS were significantly higher than CTR (all with p<0,001). PKD1&#95;TRS pts had significantly higher NGAL, CysC, Cr and Urea levels compared to PKD1&#95;AMB and PKD1&#95;WT. PKD1&#95;AMB pts had higher NGAL, CysC, Urea and Cr levels compared to PKD1&#95;WT relatives. NGAL CysC, Cr and urea values were similar between PKD1&#95;WT and CTR (p>0.05). NGAL levels were not significantly different in ADPKD patients in CKD stage II-III with mutation in PKD1 or PKD2 (86 pg/mL, IQR 60-109 vs 82 pg/mL,IQR 63-169). NGAL correlated well (all with p<0.001) with CysC (r=0.95), Cr (r=0.89), urea (r=0.76) and inversely with eGFR (r=-0.81). A strong correlation between CysC and residual renal function was observed (CysC/eGFR: r=-0.86; CysC/Cr: r=0.7; CysC/Urea: r=0.79, all with p<0.001)., Conclusion: This is the first study to evaluate plasma NGAL in the context of genotype-phenotype correlation. In ADPKD, NGAL levels were higher in patients already on Renal Replacement Therapy (RRT) compared to their affected relatives not on RRT. WT relatives had normal NGAL and CysC levels: these could be considered a better CTR group because they share the same genetic background with ADPKD subjects. No differences were found in NGAL levels between PKD1 and PKD2 patients in CKD stage II-III. Furthermore, the results indicate that NGAL correlates closely with renal function and CysC levels.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder, with a prevalence of 1:400 to 1:1000. ADPKD is genetically and clinically heterogeneous. In addition, significant intrafamilial renal disease variability is evident. The prevalence of ADPKD patients on renal replacement therapy in Italy has been reported to be 8.2%. In the dialysis population of Vicenza province (northeast Italy), in one area especially, ADPKD cases account for 13.4%. We hypothesize that this high frequency is related to a founder effect in this geographically isolated population. Since April 2007 we have studied the characteristics of ADPKD patients and the presence of haplotypes shared by several families. The clinical profile of patients in the Vicenza province is similar to that described in the literature but there is a high prevalence of ADPKD in several isolated areas. These areas are characterized by the presence of three distinct haplotypes, suggesting a strong lineage-specific gene.