15-year-change of phenotype and prognosis in non-dialysis CKD patients referred to a nephrology clinic.

PURPOSE: Changes over time of phenotype and prognosis in CKD patients starting nephrology care are undefined. This information is critical to correctly plan and optimize healthcare resources and clinical management in tertiary care. METHODS: We performed a long-term observational cohort study including 2,866 non-dialysis CKD patients newly referred to our nephrology clinic from 2004 to 2018. Three cohorts were constituted based on 5-year calendar intervals (2004-2008, 2009-2013, and 2014-2018). The changes over time of main demographic, clinical and laboratory characteristics were compared among the three cohorts. We also compared between cohorts the risk of renal death (combined endpoint of renal replacement therapy-RRT, or death before RRT) as well as of the single components (RRT or death). RESULTS: Across the three cohorts, we detected a significant increase in the prevalence of age ≥ 75 years (from 22.0 to 28.4%), male gender (from 53.1 to 62.1%), diabetes (from 32.6 to 39.5%), severe proteinuria ≥ 500 mg/24 h (from 46.9 to 52.4%). Mean eGFR at referral declined from 56.8 ± 27.0 to 49.6 ± 26.1 mL/min/1.73m2. Incidence of renal death significantly declined over time (5.36, 3.22 and 4.54/100 pts-year in 2004-2008, 2009-2013 and 2014-2018 cohorts, respectively). As compared with patients referred in 2004-2008, adjusted risk of renal death was lower in patients referred in 2009-2013 (HR 0.49, 95%CI 0.34-0.69) and 2014-2018 (HR 0.61, 95%CI 0.45-0.84). Similar results were obtained for RRT, while mortality did not change over time. CONCLUSIONS: In the last 15 years, phenotype of newly referred CKD patients has remarkably changed with increasing frequency of older patients and more severe disease; however, renal survival improved suggesting greater efficacy of nephrology care.

Area Deprivation and Risk of Death and CKD Progression: Long-Term Cohort Study in Patients under Unrestricted Nephrology Care.

BACKGROUND: Area deprivation index (ADI) associates with prognosis in non-dialysis CKD. However, no study has evaluated this association in CKD patients under unrestricted nephrology care. METHODS: We performed a long-term prospective study to assess the role of deprivation in CKD progression and mortality in stage 1-4 CKD patients under regular nephrology care, living in Naples (Italy). We used ADI calculated at census block levels, standardized to mean values of whole population in Naples, and linked to patients by georeference method. After 12 months of "goal-oriented" nephrology treatment, we compared the risk of death or composite renal outcomes (end-stage kidney disease or doubling of serum creatinine) in the tertiles of standardized ADI. Estimated glomerular filtration rate (eGFR) decline was evaluated by mixed effects model for repeated eGFR measurements. RESULTS: We enrolled 715 consecutive patients (age: 64 ± 15 years; 59.1% males; eGFR: 49 ± 22 mL/min/1.73 m2). Most (75.2%) were at the lowest national ADI quintile. At referral, demographic, clinical, and therapeutic features were similar across ADI tertiles; after 12 months, treatment intensification allowed better control of hypertension, proteinuria, hypercholesterolaemia, and anaemia with no difference across ADI tertiles. During the subsequent long-term follow-up (10.5 years [interquartile range 8.2-12.6]), 166 renal events and 249 deaths were registered. ADI independently associated with all-cause death (p for trend = 0.020) and non-cardiovascular (CV) mortality (p for trend = 0.045), while CV mortality did not differ (p for trend = 0.252). Risk of composite renal outcomes was similar across ADI tertiles (p for trend = 0.467). The same held true for eGFR decline (p for trend = 0.675). CONCLUSIONS: In CKD patients under regular nephrology care, ADI is not associated with CKD progression, while it is associated with all-cause death due to an excess of non-CV mortality.

Sodium toxicity in peritoneal dialysis: mechanisms and "solutions".

The major trials in peritoneal dialysis (PD) have demonstrated that increasing peritoneal clearance of small solutes is not associated with any advantage on survival, whereas sodium and fluid overload heralds higher risk of death and technique failure. On the other hand, higher sodium and fluid overload due to loss of residual kidney function (RKF) and higher transport membrane is associated with poor patient and technique survival. Recent experimental studies also show that, independently from fluid overload, sodium accumulation in the peritoneal interstitium exerts direct inflammatory and angiogenetic stimuli, with consequent structural and functional changes of peritoneum, while in patients with Chronic Kidney Disease sodium stored in interstitial skin acts as independent determinant of left ventricular hypertrophy. Noteworthy, this tissue pool of sodium is modifiable being removed by dialysis. Therefore, novel PD strategies to optimize sodium removal, including the use of bimodal and/or low-sodium solutions, are actively tested. Nonetheless, a holistic approach aimed at preserving peritoneal function and the kidney may represent the key of therapy success in the hard task of preserving adequate sodium balance in PD patients. In this review, we describe the available evidence on sodium toxicity in PD, either related or unrelated to fluid overload, and we also discuss about possible "solutions" to preserve or restore sodium balance in PD patients.

[Peritoneal dialysis catheter infection with abscess of the abdominal wall in a ADPKD patient].

Infections to the peritoneal catheter are common in Peritoneal Dialysis (PD). We report the clinical case of a 49-year-old male patient in PD, who showed an atypical manifestation of tunnel infection caused by Staphylococcus aureus. The infection was characterized by a little abscess, on the left pararectal abdominal line, 6 cm far from exit-site of the peritoneal catheter. The diagnosis was made using ultrasonography (US), which showed a fistulous communication from subcutaneous cuff to the skin. We treated the infection conservatively by performing cuff-shaving and drainage of the abscess, associated to antibiotic therapy (teicoplanin). Due to the persistence of the infection, we added oral and topical rifampicin, and advanced medication with freez-dried collagen plant impregnated with extended-release gentamicin. The complete resolution of the infection allowed us to avoid removing the catheter.

[Role of Ambulatory Blood Pressure Monitoring (ABPM) in chronic kidney patients: a review].

About 90%of patients with chronic kidney disease (CKD) have arterial hypertension; the main international guidelines recommend maintaining blood pressure (BP) values below 130/80 mmHg to reduce the cardio-renal risk in this population. Twenty-four-hour Ambulatory Blood Pressure Monitoring (ABPM) is the golden standard for the identification of the BP profiles and patterns, as well as for the assessment of the circadian rhythm and BP variability. The correct interpretation of ABPM allows to optimize anti-hypertensive treatment and to reduce cardio-renal risk in CKD patient. In fact, in patients with CKD, the ABPM has a greater role in terms of renal and cardio-vascular prognosis when compared to clinical BP measurements. Patients with ABPM in target present a low cardio-renal risk, regardless of clinical BP values; on the contrary, if the clinical PA is normal and the ABPM not in target, this risk increases significantly. Moreover, in the CKD population, non-dipping is associated with a higher risk of cardiovascular events and end stage renal disease (ESRD), making identifying nocturnal hypertension greatly important. Therefore, ABPM is an instrument of primary importance in the diagnostic and therapeutic work-out of renal patients.

[Infected hepatic cyst in ADPKD patient in peritoneal dialysis].

Renal and hepatic cysts infections are among the most important infectious complications of ADPKD and often require hospitalization. Liver cysts are even more complex than renal cysts and their diagnosis and treatment are quite controversial. We report the case of a 58-year-old patient with ADPKD undergoing peritoneal dialysis treatment. He presented fever and severe asthenia and was diagnosed with a hepatic cyst infection. Given the presence of the peritoneal catheter, and in order to facilitate the targeted treatment of the infection, we administered antibiotics (ceftazidime and teicoplanin) in the bags used for peritoneal dialysis exchanges for 4 weeks, obtaining the complete disappearance of symptoms and laboratory and ultrasound alterations. Intraperitoneal antibiotics administration in the treatment of infected hepatic cysts represents an effective and safe therapeutic alternative, never described in literature so far.

Incremental dialysis in ESRD: systematic review and meta-analysis.

BACKGROUND: Incremental dialysis may preserve residual renal function and improve survival in comparison with full-dose dialysis; however, available evidence is limited. We therefore compared all-cause mortality and residual kidney function (RKF) loss in incremental and full-dose dialysis and time to full-dose dialysis in incremental hemodialysis (IHD) and incremental peritoneal dialysis (IPD). METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with ESRD starting IHD and IPD. We identified in PubMed and Web of Science database all cohort studies evaluating incremental dialysis evaluating three outcomes: all-cause mortality, RKF loss, time to full dialysis. IPD was defined as < 3 daily dwells in Continuous Ambulatory Peritoneal Dialysis and < 5 sessions per week in Automated Peritoneal Dialysis, while IHD was defined as < 3 HD sessions per week. RESULTS: 22 studies (75,292 participants), 15 in HD and 7 in PD, were analyzed. Mean age at dialysis start was 62 and 57 years in IHD and IPD subjects, respectively. When compared to full dose, incremental dialysis (IHD or IPD) had an overall mortality risk of 1.14 [95% CI 0.85-1.52] with high heterogeneity among studies (I2 86%, P < 0.001), and lower mean RKF loss (- 0.58 ml/min/months, 95% CI 0.16-1.01, P = 0.007). Overall, time to full-dose dialysis was 12.1 months (95% CI 9.8-14.3) with no difference between IHD and IPD (P = 0.217). CONCLUSIONS: Incremental dialysis allows longer preservation of RKF thus deferring full-dose dialysis, by about 1 year in HD and PD, with no increase in mortality risk. Large and adequate studies are needed to confirm these findings.

Competing-Risk Analysis of Death and End Stage Kidney Disease by Hyperkalaemia Status in Non-Dialysis Chronic Kidney Disease Patients Receiving Stable Nephrology Care.

Hyperkalaemia burden in non-dialysis chronic kidney disease (CKD) under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalaemia (serum potassium, sK ≥ 5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of end stage kidney disease (ESKD) and death after visit 2. Age was 65 ± 15 years, eGFR 35 ± 17 mL/min/1.73 m², proteinuria 0.40 (0.14⁻1.21) g/24 h. In the two visits sK was 4.8 ± 0.6 and levels ≥6 mEq/L were observed in 4%. Hyperkalaemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis (sub-hazard ratio-sHR, 95% Confidence Interval-CI) evidenced that new onset (sHR 1.34, 95% CI 1.05⁻1.72) and persistent (sHR 1.27, 95% CI 1.02⁻1.58) hyperkalaemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalaemia status is common (37%) and predicts per se higher ESKD risk but not mortality.

[Hyperkalemia treatment in chronic kidney disease patients: overview on new K binders and possible therapeutic approaches]. / Iperkaliemia nel paziente con Malattia Renale Cronica in trattamento conservativo: overview sui nuovi chelanti e sui possibili approcci terapeutici

Hyperkalaemia is a common complication in patients with nondialysis Chronic Kidney Disease (CKD). It is associated with weakness, paralysis, arrhythmias and increased mortality. Higher serum potassium levels refractory to treatment is one of the most frequent reasons to initiate immediately renal replacement treatment in advanced stages of CKD. Hyperkalaemia is also indirectly associated with the progression of CKD; in fact higher serum potassium levels may lead to withdrawal of renin-angiotensin-system inhibiting drugs that currently represent the most effective tools to postpone ESRD. It is therefore essential to identify patients at higher risk of increase of serum K and to implement therapeutic interventions aimed at preventing and treating hyperkalaemia, such as diet modifications and greater use of diuretics and cation exchange resins. Sodium and calcium-polystyrenesulfonate (SPS) are the resins currently available in Italy. However, few studies showed that SPS is efficacious to reduce serum K and is associated with increased risk of severe adverse effects. Patiromer and ZS-9 represent a significant pharmacological progress in the treatment of hyperkalemia. Indeed, recent studies showed that these novel resins are efficient to reduce serum levels of K with minor occurrence of side effects than polystyrensulfonates. Furthermore, Patiromer, sodium free agent, might have a further advantage in CKD patients, reducing the salt intake in these patients. In addition, ZS-9, being fast-acting drug, might be used also in the treatment of acute hyperkalaemia.

Dietary Salt Restriction in Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: A clear evidence on the benefits of reducing salt in people with chronic kidney disease (CKD) is still lacking. Salt restriction in CKD may allow better control of blood pressure (BP) as shown in a previous systematic review while the effect on proteinuria reduction remains poorly investigated. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the effects of low versus high salt intake in adult patients with non-dialysis CKD on change in BP, proteinuria and albuminuria. RESULTS: Eleven RCTs were selected and included information about 738 CKD patients (Stage 1⁻4); urinary sodium excretion was 104 mEq/day (95%CI, 76⁻131) and 179 mEq/day (95%CI, 165⁻193) in low- and high-sodium intake subgroups, respectively, with a mean difference of −80 mEq/day (95%CI from −107 to −53; p <0.001). Overall, mean differences in clinic and ambulatory systolic BP were −4.9 mmHg (95%CI from −6.8 to −3.1, p <0.001) and −5.9 mmHg (95%CI from −9.5 to −2.3, p <0.001), respectively, while clinic and ambulatory diastolic BP were −2.3 mmHg (95%CI from −3.5 to −1.2, p <0.001) and −3.0 mmHg (95%CI from −4.3 to −1.7; p <0.001), respectively. Mean differences in proteinuria and albuminuria were −0.39 g/day (95%CI from −0.55 to −0.22, p <0.001) and −0.05 g/day (95%CI from −0.09 to −0.01, p = 0.013). CONCLUSION: Moderate salt restriction significantly reduces BP and proteinuria/albuminuria in patients with CKD (Stage 1⁻4).

[Hyperuricaemia and Chronic Kidney Disease].

Hyperuricemia is defined as serum uric acid values greater than 6 mg/dl and could occur either due to hyperproduction or as a result of reduced renal excretion, which exceeds gut compensation. In Italy, prevalence is around 12% of the general population and increases in renal disease up to 60%. Recent experimental studies demonstrated a role of uric acid in the development of arterial hypertension and systemic arteriosclerosis, with an increase in cardiovascular risk. It also appears from observational studies that high uric acid is an independent risk factor associated with de novo onset of chronic kidney disease after adjustment of main confounding variables. Hyperuricemic subjects treated with febuxostat, a selective inhibitor of xantino-oxidase, showed in RCTs a better control of hyperuricaemia in comparison with those receiving allopurinol. Moreover, observational studies indicate that urate lowering treatment could be helpful in reducing cardiovascular events as well as in slowing the progression of chronic kidney disease; randomized controlled studies, designed to assess as primary outcome the nephroprotective effect of urate lowering treatment, are in progress.