[Oxalobacter formigenes - use of the colon microbiome in the prevention of kidney stones]. / Oxalobacter formigenes ­ wykorzystanie mikrobiomu jelita grubego w profilaktyce kamicy nerkowej.

The number of calcium oxalate urolithiasis is increasing every year, especially in highly developed countries. The most common causes of precipitation are hyperoxaluria and hypercalciuria. The reason for increased oxalate excretion may be genetic defects of hepatic enzymes (primary hyperoxaluria), disturbances in metabolism or absorption of oxalate and changes in the composition of the intestinal microflora in the form of deficiency of oxalate metabolizing bacteria e.g. Oxalobacter formigenes. This bacterium has been the scientific focus of attention in recent years due to numerous reports on its impact on the reduction of oxaluria, resulting in a decreased recurrence risk of calcium oxalate stones by up to 70%. In recent years, attempts have been made to create a probiotic drug, the main element of which is O. formigenes.

[Water-sodium homeostasis in hemodialysis - the eternal problem in nephrology practice]. / Homeostaza wodno-sodowa w hemodializie ­ odwieczny problem w praktyce nefrologicznej.

The kidney is an organ that maintains the body's sodium and water balance and plays a significant role in blood pressure regulation. Chronic kidney disease (CKD) and a progressive loss of its function, among others, leads to sodium and water retention and, as a consequence, to arterial hypertension. The supply of salt and fluids delivered with the diet significantly affects the cardiovascular system's functioning particularly in hemodialysis patients. The critical element in clinical care is maintaining appropriate water and electrolyte homeostasis. Overhydration is manifested as oedema and blood preassure increase, but a more accurate assessment of subtle variations is possible by measuring bioelectric impedance (BIA), which determines the extracellular water index (ECW). Actions to maintain euvolemia include limiting sodium and fluid intake, regular assessment of "dry" body weight, proper selection of ultrafiltration (UF), correction of sodium concentration, and dialysate temperature.

Comparison of Different Methods of Urinary Protein Excretion Measurement: Is the King Really Dead?

INTRODUCTION: Assessing proteinuria is of uttermost importance for a nephrologist. It is often indispensable to accurately quantify the amount of protein lost, hence complicated and time-consuming urine collections (the gold standard or "king" of methods - 24-h protein excretion rate [PER]) are often replaced by spot urinary protein to creatinine ratio (PCR). The aim of the study was to determine whether the latter can reliably compare to the gold standard and whether "timing" of a spot urine sample is essential. METHODS: We performed a prospective, single-center study of 143 consecutive adult patients with glomerular proteinuria (a total of 187 cases). Protein and creatinine concentration was measured in 3 consecutive urine samples (starting with the first morning void) and a simultaneous 24-h urine collection. Agreement between 24-h PER and PCR was evaluated with Bland-Altman plots. RESULTS: Compared to PER 3 consecutive PCRs were 0.86, 0.66, and 0.50 higher with wide limits of agreement respectively. The bias between 2 methods was influenced by sex, CKD stage, albumin concentration and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment. In 24 participants, in whom at least 2 measurements at different time points were available, only 88% of differences were lower than the calculated repeatability coefficient. CONCLUSIONS: Unfortunately although random PCR correlates with 24-h protein excretion, the scatter of differences increases as 24-h proteinuria rises (without any significant effect of the sampling time). The observed lack of agreement makes PCR an unsuitable parameter to correctly quantify proteinuria; it is also not useful for monitoring the amount of daily proteinuria in the same patient. Therefore, while searching for new markers, nephrologists can only say: "long live the king!"

C-terminal and intact FGF23 in critical illness and their associations with acute kidney injury and in-hospital mortality.

BACKGROUND: FGF23 proved its value in prognostication of cardiovascular events and mortality among renal patients and general population. Limited data exist whether FGF23 may have any use in prediction of negative outcomes among critically ill patients admitted to intensive care unit (ICU). METHODS: Single center cohort study performed among patients admitted to ICU. The primary exposure was FGF23 plasma concentration measured within 24 h of ICU admission. The primary outcome was incident Acute Kidney Injury (AKI) and in-hospital mortality during the ICU stay. RESULTS: The study enrolled 79 patients admitted to ICU. C-terminal FGF23 (cFGF23) but not intact FGF23 (iFGF23) concentration was significantly elevated in patients, who acquired AKI and non-survivors (p < .001). ROC analysis of cFGF23 yielded an AUC of 0.81 and 0.85 for prediction of incident AKI and death during ICU stay, respectively. Multivariate analysis showed higher odds for AKI (OR 1.80; 95% CI 1.10-2.96) and in-hospital mortality (OR 2.85; 95% CI 1.60-5.06) for one unit increase of log transformed cFGF23. CONCLUSIONS: cFGF23 measurement may serve as a novel biomarker for incident AKI and death among critically ill patients.

Clinicopathologic correlations of renal pathology in the adult population of Poland.

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

Effects of 17ß-estradioland raloxifene on endothelial OPG and RANKL secretion.

OBJECTIVES: This study aims to asses the effects of estradiol vs. raloxifene on the levels of osteoprotegerin and soluble Receptor Activator of Nuclear Factor kB Ligand (sRANKL) in Human Umbilical Vein Endothelial Cells (HUVEC) culture in standard and calcifying medium. MATERIAL AND METHODS: Human Umbilical Vein Endothelial Cells were isolated from human umbilical vein by standard method. The supernatant concentrations of osteoprotegerin (OPG) and sRANKL (ELISA) were determined after incubation with glicerophosphate, estradiol , raloxifene, glicerophoshate and estradiol, glicerophosphate and raloxifene in comparison with control group at four designated time points (0, 1, 2 and 4 days of incubation). RESULTS: Incubation of estradiol with HUVEC colony lowered the OPG level significantly after day 2 and 4. Meantime, the level of sRANKL was stable. Raloxifene added to standard growth medium also significantly lowered OPG concentration after day 4 only, with no impact on sRANKL concentration. When added to calcifying medium, both estradiol and raloxifene significantly changed OPG level during the experiment. In all treated groups OPG levels were lower than in groups exposed to calcifying medium only. Neither estradiol, nor raloxifene changed sRANKL levels during the experiment. CONCLUSIONS: Estradiol and raloxifene affect OPG secretion from endothelial cells in vitro which may suggest their modifying role in pathogenesis of vascular calcification in postmenopausal women.

[Skin cancers in kidney transplant recipients].

Kidney transplantation is the best treatment for end-stage renal failure. It prolongs the patient's life, improves quality of life and reduces costs associated with renal replacement therapy. Increasingly, newer immunosuppressive regimens allow for the proper functioning of the transplanted organ for many years. The progress in transplantation, qualification patients in older age for the procedure and longer survival of kidney graft lead to an increase in the number of patients receiving immunosuppressive drugs. They are exposed to various side effects associated with long-term suppression of the immune system, including an increased risk of cancer development. The most common malignancies (40- 50%) diagnosed in renal transplant recipients are skin cancers. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common types of tumors occurring in this population. The use of immunosuppression resulted in the increase of the incidence of tumors that in the general population are relatively rare such as melanoma, Merkel cell cancer, Kaposi's sarcoma, anogenital cancer as well as sebaceous carcinoma.

Overuse of proton pump inhibitors and its consequences.

Direct inhibition of H+ ion excretion to the gastric lumen makes proton pump inhibitors (PPI) the most effective drugs against gastric acid-related diseases. Over recent years usage of proton pump inhibitors has increased dramatically. Due to the low costs, high efficacy and rarity of adverse effects, their use is prevalent and often it does not correspond with existing medical guidelines. The literature lists stress ulcer prophylaxis among patients with low risk of bleeding, routine 'gastroprotective' medication during treatment and non-specific abdominal symptoms as the most common patterns of off-label PPI use. This article summarizes the influence of PPI therapy on gastric mucosa, absorption and occurrence of adverse effects. The authors note that their low awareness among physicians contributes to wide and imprudent use of drugs of this group.

[Risk factors for cancer development in patients after kidney transplantation].

Kidney transplantation in patients with ESRD (end-stage renal disease) improves quality of life and is associated with an increase in both survival rates and the reduction in medical costs compared with patients waiting for a transplant as well as dialysis population. Cancers, next to the cardiovascular disease and infection, present as one of the most common causes of kidney transplant recipients deaths. Incidence of neoplasm after kidney transplantation is between 2.3 and 31%. Risk factors for carcinogenesis after transplantation can be divided into three main groups which include traditional factors (genetic predisposition, exposure to UVA and UVB radiation, smoking, abuse of painkillers, cancer in the pretransplant period), factors connected with kidney disease (cause and treatment of kidney failure) and related to transplantation (immunosuppressive regimen, chronic viral infection, cancer transition with graft). Immunosuppressive treatment undoubtedly has a huge impact on the development of tumours in patients after transplantation. It is to be remembered to include mTOR inhibitors in immunosuppressive regimen in patients with a history of cancer. In kidney recipients the frequency of reactivation as well as de novo infection of oncogenic virus is increased, particularly: EBV (Epstein-Barr virus), HBV (hepatitis type B virus), HCV (hepatitis type C virus), HPV (human papilloma virus) i HHV8 (human herpes virus type 8). An important aspect is the awareness of patients about the increased risk of cancer development and necessity of respecting and applying of preventive recommendations.

Automated Peritoneal Dialysis With Remote Patient Monitoring: Clinical Effects and Economic Consequences for Poland.

OBJECTIVES: Remote patient monitoring (RPM) of patients treated with automated peritoneal dialysis (APD) at home allows clinicians to supervise and adjust the dialysis process remotely. This study aimed to review recent scientific studies on the use of RPM in patients treated with APD and based on extracted relevant data assess possible clinical implications and potential economic value of introducing such a system into practice in Poland. METHODS: A systematic literature review was performed in the MEDLINE, EMBASE, and Cochrane databases. The model of clinical effects and costs associated with APD was built as a cost-effectiveness analysis with a 10-year time horizon from the Polish National Health Fund perspective. Cost-effectiveness analysis compared 2 strategies: APD with RPM versus APD without RPM. RESULTS: Thirteen publications assessing the clinical value of RPM among patients with APD were found. The statistical significance of APD with RPM compared with APD without RPM was identified for the main clinical outcomes: frequency and length of hospitalizations, APD technique failure, and death. An incremental cost-effectiveness ratio was equal to €27 387 per quality-adjusted life-year. The obtained incremental cost-effectiveness ratio is below the willingness-to-pay threshold for the use of medical technologies in Poland (€36 510 per quality-adjusted life-year), which means that APD with RPM was a cost-effective technology. CONCLUSIONS: RPM in patients starting APD is a clinical option that is worth considering in Polish practice because it has the potential to decrease the frequency of APD technique failure and shorten the length of hospitalization.

Pharmacological Nephroprotection in Non-Diabetic Chronic Kidney Disease-Clinical Practice Position Statement of the Polish Society of Nephrology.

Chronic kidney disease (CKD) is a modern epidemic worldwide. Introducing renin-angiotensin system (RAS) inhibitors (i.e., ACEi or ARB) not only as blood-pressure-lowering agents, but also as nephroprotective drugs with antiproteinuric potential was a milestone in the therapy of CKD. For decades, this treatment remained the only proven strategy to slow down CKD progression. This situation changed some years ago primarily due to the introduction of drugs designed to treat diabetes that turned into nephroprotective strategies not only in diabetic kidney disease, but also in CKD unrelated to diabetes. In addition, several drugs emerged that precisely target the pathogenetic mechanisms of particular kidney diseases. Finally, the role of metabolic acidosis in CKD progression (and not only the sequelae of CKD) came to light. In this review, we aim to comprehensively discuss all relevant therapies that slow down the progression of non-diabetic kidney disease, including the lowering of blood pressure, through the nephroprotective effects of ACEi/ARB and spironolactone independent from BP lowering, as well as the role of sodium-glucose co-transporter type 2 inhibitors, acidosis correction and disease-specific treatment strategies. We also briefly address the therapies that attempt to slow down the progression of CKD, which did not confirm this effect. We are convinced that our in-depth review with practical statements on multiple aspects of treatment offered to non-diabetic CKD fills the existing gap in the available literature. We believe that it may help clinicians who take care of CKD patients in their practice. Finally, we propose the strategy that should be implemented in most non-diabetic CKD patients to prevent disease progression.

The influence of calcitriol and methylprednisolone on podocytes function in minimal change disease in vitro model.

Minimal change disease (MCD), considered one of the major causes of nephrotic syndrome, is a complex pathological condition with disturbances in podocytes' foot processes. Numerous studies suggested the essential role of vitamin D3 in maintaining proper glomerulus function. However, the data on direct potential of that compound in reference to podocytes are scarce. Thus, here we assessed the influence of calcitriol (active vitamin D3) on podocyte function, apart from commonly used steroids (methylprednisolone). CIHP-1 podocyte cell line was used to implement the LPS-PAN-induced MCD in vitro model. Viability, podocyte-related slit diaphragm proteins, morphology, function as a barrier was evaluated using flow cytometry, RT-PCR, confocal microscopy, and TEER analysis. Calcitriol or methylprednisolone did not affect cell viability. Podocyte-related proteins demonstrated different responses to in vitro treatment compared to previously reported changes in total glomeruli. Podocyte morphology was partially restored in the presence of the tested compounds. In addition, TEER analysis revealed improvement of LPS-PAN-induced cells' function as a barrier when vitamin D3 or steroid was used. In conclusion, a significant potential for modulation of MCD in vitro model podocytes with calcitriol or selected steroids was reported. Further studies on vitamin D3 in context of podocyte-related phenomenon accompanying MCD are of great importance.

Nephro-oncology: clinical and biochemical aspects of kidney disease and cancer.

Onco-nephrology is a new field of medicine which combines many aspects of kidney injury in cancer patients and cancers in patients with kidney disease. This connection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, numerous paraneoplastic syndromes and an increased rate cancers in dialysis and transplanted patients. The appropriate laboratory assessment of the kidney function allows to optimize chemotherapy and thus minimizes the risk of complications. This article focuses on acute kidney injury (AKI), chronic kidney disease (CKD), various electrolyte and acid-base disorders, the most common cancers after kidney transplantation and the kidney disorders associated with HSCT (hematopoietic stem cell transplantation). The possibility of the application of novel cancer therapy, such as cancer immunotherapy and proton therapy in transplant recipients was also discussed.

Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

OBJECTIVE: To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN). METHODS: A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26. RESULTS: A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7-95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9-75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5-10%) and severe infections (10% vs. 4.8-5.0%) were reported with 240 mg BI 655064. CONCLUSION: The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.

The mechanism of vascular calcification - a systematic review.

Calcification of vessels reduces their elasticity, affecting hemodynamic parameters of the cardiovascular system. The development of arterial hypertension, cardiac hypertrophy, ischemic heart disease or peripheral arterial disease significantly increases mortality in patients over 60 years of age. Stage of advancement and the extent of accumulation of calcium deposits in vessel walls are key risk factors of ischemic events. Vascular calcification is an active and complex process that involves numerous mechanisms responsible for calcium depositions in arterial walls. They lead to increase in arterial stiffness and in pulse wave velocity, which in turn increases cardiovascular disease morbidity and mortality. In-depth study and thorough understanding of vascular calcification mechanisms may be crucial for establishing an effective vasculoprotective therapy. The aim of this study was to present a comprehensive survey of current state-of-the-art research into the impact of metabolic and hormonal disorders on development of vascular calcification. Due to strong resemblance to the processes occurring in bone tissue, drugs used for osteoporosis treatment (calcitriol, estradiol, bisphosphonates) may interfere with the processes occurring in the vessel wall. On the other hand, drugs used to treat cardiovascular problems (statins, angiotensin convertase inhibitors, warfarin, heparins) may have an effect on bone tissue metabolism. Efforts to optimally control calcium and phosphate concentrations are also beneficial for patients with end-stage renal disease, for whom vessel calcification remains a major problem.

Comparison of Post-Transplantation Lymphoproliferative Disorder Risk and Prognostic Factors between Kidney and Liver Transplant Recipients.

Post-transplantation lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation (SOT). Its development risk varies among organ graft recipients. In this study, retrospective data were analyzed to compare PTLD's risk and prognostic factors between adult kidney and liver transplant recipients (KTRs and LTRs, respectively). Over 15 years, 2598 KTRs and 1378 LTRs were under observation at our center. Sixteen KTRs (0.62%) and twenty-three LTRs (1.67%) were diagnosed with PTLD. PTLD developed earlier in LTRs (p < 0.001), SOT patients > 45 years old (p = 0.002), and patients receiving tacrolimus (p < 0.001) or not receiving cyclosporin (p = 0.03) at diagnosis. Tacrolimus use, male sex, and age > 45 years old significantly affected the time of PTLD onset in KTRs (hazard ratio (HR) = 18.6, 7.9 and 5.2, respectively). Survival was longer in LTRs < 45 years old (p < 0.009). LTRs were more likely than KTRs to achieve complete remission (p = 0.039). Factors affecting PTLD development and outcome differ between KTRs and LTRs; thus, these populations should be separately evaluated in future studies.

Factors Influencing Longevity of Humoral Response to SARS-CoV-2 Vaccination in Patients with End Stage Kidney Disease Receiving Renal Replacement Therapy.

COVID-19 has severely affected the population of patients with end stage renal disease. Current data have proved a two-dose vaccination schedule against SARS-CoV-2 to be effective among dialyzed patients. There are limited data on the longevity and modulating factors of humoral response after vaccination. We performed a prospective longitudinal cohort study to determine longevity of the humoral response after SARS-CoV-2 vaccine. The study included 191 adult patients on hemodialysis and peritoneal dialysis. All participants had been vaccinated with three doses, either with BNT162b2 (Pfizer-BioNTech) (n = 109) or mRNA-1273 (Moderna) (n = 82). Anti-spike protein receptor-binding domain antibodies (anti-S IgG) were assessed using SARS-CoV-2 (RBD) IgG ELISA EIA-6150 IVD assay at baseline, on the 21st day and 43rd day, before a booster dose and two weeks thereafter. We found that before vaccination, 37.7% of the cohort had anti-S IgG titres concordant with seroconversion. After two-dose vaccination, seroconversion occurred in 97% of patients. The booster dose evoked a ~12-fold increase in antibody level. Obesity increased more than two-fold the odds for a decrease in anti-S IgG. Previous COVID-19 infection enhanced longevity of the humoral response following vaccination. In patients with previous COVID-19 infection, the BNT162b2 vaccine was associated with a higher odds of anti-S IgG waning compared to the mRNA-1273 vaccine. In conclusion, we report that obesity predisposes patients to protective antibody waning, hybrid immunity enhances odds for higher anti-S IgG concentrations and vaccine efficacy may be influenced by previous SARS-CoV-2 infection. The results might provide a rationale for vaccination protocol design.

Thrombolome and Its Emerging Role in Chronic Kidney Diseases.

Patients with chronic kidney disease (CKD) are at an increased risk of thromboembolic complications, including myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. These complications lead to increased mortality. Evidence points to the key role of CKD-associated dysbiosis and its effect via the generation of gut microbial metabolites in inducing the prothrombotic phenotype. This phenomenon is known as thrombolome, a panel of intestinal bacteria-derived uremic toxins that enhance thrombosis via increased tissue factor expression, platelet hyperactivity, microparticles release, and endothelial dysfunction. This review discusses the role of uremic toxins derived from gut-microbiota metabolism of dietary tryptophan (indoxyl sulfate (IS), indole-3-acetic acid (IAA), kynurenine (KYN)), phenylalanine/tyrosine (p-cresol sulfate (PCS), p-cresol glucuronide (PCG), phenylacetylglutamine (PAGln)) and choline/phosphatidylcholine (trimethylamine N-oxide (TMAO)) in spontaneously induced thrombosis. The increase in the generation of gut microbial uremic toxins, the activation of aryl hydrocarbon (AhRs) and platelet adrenergic (ARs) receptors, and the nuclear factor kappa B (NF-κB) signaling pathway can serve as potential targets during the prevention of thromboembolic events. They can also help create a new therapeutic approach in the CKD population.

Water removal during automated peritoneal dialysis assessed by remote patient monitoring and modelling of peritoneal tissue hydration.

Water removal which is a key treatment goal of automated peritoneal dialysis (APD) can be assessed cycle-by-cycle using remote patient monitoring (RPM). We analysed ultrafiltration patterns during night APD following a dry day (APDDD; no daytime fluid exchange) or wet day (APDWD; daytime exchange). Ultrafiltration for each APD exchange were recorded for 16 days using RPM in 14 patients. The distributed model of fluid and solute transport was applied to simulate APD and to explore the impact of changes in peritoneal tissue hydration on ultrafiltration. We found lower ultrafiltration (mL, median [first quartile, third quartile]) during first and second vs. consecutive exchanges in APDDD (-61 [-148, 27], 170 [78, 228] vs. 213 [126, 275] mL; p < 0.001), but not in APDWD (81 [-8, 176], 81 [-4, 192] vs. 115 [4, 219] mL; NS). Simulations in a virtual patient showed that lower ultrafiltration (by 114 mL) was related to increased peritoneal tissue hydration caused by inflow of 187 mL of water during the first APDDD exchange. The observed phenomenon of lower ultrafiltration during initial exchanges of dialysis fluid in patients undergoing APDDD appears to be due to water inflow into the peritoneal tissue, re-establishing a state of increased hydration typical for peritoneal dialysis.