Atypical HUS with multiple complement system mutations triggered by synthetic psychoactive drug abuse: a case report.

Atypical hemolytic uremic syndrome is a rare disorder with an estimated annual incidence of about two cases per million in the adult population. It is caused by the overactivation of the alternative pathway of the complement system. The disease can be triggered by many factors, including pregnancy, viral diseases, and sepsis; approximately 30% of atypical hemolytic uremic syndrome cases are caused by unknown processes. We present a case of a patient with C3-complement system mutations and aHUS triggered by the use of a new synthetic psychoactive drug.

Performance of Derived Laboratory Biomarkers with Regard to 30-Day Mortality in Kidney Transplant Recipients with COVID-19.

There are limited data on the performance of laboratory-derived biomarkers in kidney transplant recipients (KTR) with COVID-19. This observational study enrolled 65 KTR with COVID-19 who were treated at the University Hospital of Split up to March 2022. Laboratory-derived biomarkers (neutrophile-to-lymphocyte (NLR) ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, De Ritis ratio, C-reactive protein (CRP)-to-albumin ratio, lactate dehydrogenase (LDH)-to-hemoglobin ratio, CRP-to-lymphocyte ratio, red cell distribution width-to-albumin ratio, platelet-to-albumin ratio, D-Dimer-to-albumin ratio, D-Dimer-to-NLR ratio, LDH-to-albumin ratio, and LDH-to-white blood cell (WBC) ratio) were calculated, and their performance with regard to 30-day mortality was determined. Mortality events occurred in 12 patients (18.5%), which was significantly associated with increased De Ritis (HR 3.83, 95% CI 1.57-9.35, p = 0.003), CRP-to-albumin (HR 1.36, 95% CI 1.13-1.64, p = 0.001), LDH-to-hemoglobin (HR 1.44, 95% CI 1.07-1.92, p = 0.015), CRP-to-lymphocyte (HR 1.03, 95% CI 1.01-1.07, p = 0.003), D-dimer-to-albumin (HR 4.94, 95% CI 1.38-7.24, p = 0.038), LDH-to-albumin (HR 1.20, 95% CI 1.05-1.36, p = 0.008), and LDH-to-WBC (HR 1.03 95% CI 1.01-1.05, p = 0.024) ratios. Out of these, the best area-under-the-curve (AUC) values were achieved with De Ritis (AUC 0.691), CRP-to-albumin (AUC 0.764), LDH-to-hemoglobin (AUC 0.877), CRP-to-lymphocyte (AUC 0.739), and LDH-to-albumin (AUC 0.827) ratios, while the best discrimination displayed LDH-to-hemoglobin ratio (Harrell's C 0.808 and Somers' D 0.616). The overall calibration was satisfactory for all models. Derived laboratory biomarkers such as the de Ritis, CRP-to-albumin, LDH-to-hemoglobin, CRP-to-lymphocyte, and LDH-to-albumin ratios show significant association and discrimination with all-cause mortality in KTR with COVID-19, suggesting its potential risk stratification role.

Rapidly progressive IgA nephritis and sarcoidosis.

Renal sarcoidosis frequently causes granulomatous interstitial nephritis, but clinically relevant nephritis is uncommon. IgA nephropathy caused by sarcoidosis is usually associated with milder stages of renal dysfunction, and only one case of rapidly progressive IgAN has been reported to date. We present an interesting case of a patient with a rapidly progressive form of IgA nephropathy caused by sarcoidosis that was successfully treated.  DOI: 10.52547/ijkd.7027.

Association of the novel CROW-65 risk score and mortality in hospitalized kidney transplant recipients with COVID-19 : A retrospective observational study.

BACKGROUND: Kidney transplant recipients (KTR) are a group of patients with heterogeneous risks for adverse outcomes with COVID-19, but risk stratification tools in this patient group are lacking. METHODS AND PARTICIPANTS: This retrospective observational, hypothesis-generating study included 49 hospitalized adult KTR patients with COVID-19 at the University Hospital of Split (August 2020 to October 2021) and evaluated the performance of novel risk score CROW-65 (age, Charlson Comorbidity Index [CCI] lactate dehydrogenase to white blood cell [LDH:WBC] ratio, and respiratory rate oxygenation [ROX index]). The primary outcome of the study was 30-day postdischarge all-cause mortality. RESULTS: A total of 8 fatal events (16.3%) occurred during the study follow-up. When comparing CROW-65 by survival status, it was significantly increased in patients with fatal event (P < 0.001). Using the Cox proportional hazards regression analysis, the CROW-65 risk score showed statistically significant association with mortality (HR 1.11, 95% CI 1.01-1.23, P = 0.027), while receiving operator characteristics (ROC) showed significant discrimination of all-cause mortality with an AUC of 0.85 (95% CI 0.72-0.94, P < 0.001), and satisfactory calibration (χ2 4.91, P = 0.555 and Harrell's C 0.835). Finally, survival Kaplan-Meier analysis confirmed significantly higher cumulative incidence of mortality with increasing risk score tertiles and curve separation after 13 days (P = 0.009). CONCLUSION: A novel risk score CROW-65 showed significant association with all-cause mortality in KTR yielding important hypothesis-generating findings. Further powered studies should reassess the performance of CROW-65 risk score in this population, including predictability, calibration and discrimination.

Expression of Pannexin 1 in the Human Kidney during Embryonal, Early Fetal and Postnatal Development and Its Prognostic Significance in Diabetic Nephropathy.

Pannexins are transmembrane glycoproteins that constitute channels involved in purinergic signaling through ATP release from cells in various physiological and pathological processes. In this study, the distribution of Panx1 expression in different cell populations of healthy postnatal human kidneys and during human embryonic and early fetal development was investigated by double immunohistochemistry. In addition, the glomerular and tubular expression of Panx1 was examined in patients with type 2 diabetes mellitus (DM2) and the control group, and renal Panx1 expression was correlated with serum creatinine. In the 6th week of embryonic development (DW), Panx1 expression was found in mesonephric glomeruli and mesonephric tubules. At the transition from 6th to 7th DW, Panx1 immunoreactivity was found in the mesonephric tubules and mesonephric duct, as well as in the metanephric ureteric bud and ampullae. In the 7th DW, strong Panx1 immunoreactivity was observed in the developing ureteric bud in the metanephros, whereas no Panx1 immunoreactivity was found in the metanephric cup. In the 8th DW, Panx1 expression was also found in the ureteric bud of the metanephros, the renal vesicle and comma-shaped nephron, and the epithelial cells of Bowman's capsule. Expression of Panx1 was found at an early stage in both the paramesonephric duct and the mesonephric duct and diminished toward the 8th DW. During the 6th-10th DW, colocalization of Panx1 with alpha smooth actin (aSMA) was found in developing blood vessels. In the postnatal kidney, strong Panx1 immunoreactivity was present in medullary and cortical collecting duct cells, renin-producing cells, and proximal tubules. Very weak Panx1 immunoreactivity was found in certain distal tubule cells and the thin descending limbs of the loop of Henle. Panx1 immunoreactivity was also found in nephrin-immunoreactive podocytes. Panx1 was not colocalized with aSMA immunoreactivity in the vessels of the postnatal human kidney, but it was present in the endothelium. A significant positive correlation was found between Panx1 expression in glomeruli and serum creatinine only in diabetic patients and was not found in the nondiabetic group. The spatiotemporal expression of Panx1 during the early stages of human kidney development supports its possible role in cellular differentiation, migration, and positioning in the developing human kidney. In addition, our data suggest that glomerular Panx1 expression is a potential indicator of worsening renal function in patients with type 2 diabetes.

Relationship of a food intake during hemodialysis and symptomatic intradialytic hypotension.

INTRODUCTION: Intradialytic hypotension is the most common complication during hemodialysis and is associated with increased cardiovascular disease, mortality, and overall hospital admissions. We analyzed the influence of food intake during hemodialysis on intradialytic hypotension. METHODS: A total of 105 patients treated with chronic hemodialysis were observed for 8 weeks-4 weeks with a meal during hemodialysis and 4 weeks without a meal. FINDINGS: A statistically significant decrease of hypotensive events (p < 0.001) and cramping episodes (p = 0.035) was observed during a 4-week period without a meal. Patients who were particularly susceptible to intradialytic hypotension were those who were diabetic, had low urinary excretion, and were treated with hemodialysis for a long time. On a follow up, there was a significant increase in serum albumin after 3 months (p = 0.01) and 6 months (p = 0.036) despite meal withdrawal during hemodialysis. DISCUSSION: Fasting during hemodialysis may cause a significantly lower frequency of intradialytic hypotension and cramping episodes without affecting the nutritional status.

Depression and serum interleukin-6 levels in patients on dialysis.

BACKGROUND: Depression is a common psychiatric problem in patients undergoing dialysis. Several studies have been performed to validate the association between depression and inflammation in haemodialysis patients. The levels of proinflammatory cytokines are increased in chronic renal failure patients, as in depression. The objective of this study was to compare the incidence of depression in the patients on dialysis (on hemodialysis /HD/ and on continuous ambulatory peritoneal dialysis /CAPD/), and a relationship between depression and the presence of inflammation. SUBJECTS AND METHODS: 88 patients (52 on HD and 36 on CAPD) were enrolled in this study. Depressive symptoms were measured with the Beck Depression Inventory (BDI). The BDI is a 21-item self-report instrument, and the elevated symptoms of depression were defined as a BDI score ≥16. HD patients were treated with high-flux polysulphone biocompatible dialyzers and CAPD patients were treated with usual dwell time (4-6 hours during the day and 8-10 hours at night). The presence of an inflammatory state was assesded by determinations of plasma interleukin-6 (IL-6) levels. RESULTS: Depression (BDI ≥16) was present in 28.4% of dialysis patients, 35% of patients on hemodialysis (HD) and 18.1% of patients on continous ambulatory peritoneal dialysis (CAPD). The BDI score was significantly lower in CAPD patients comparing to HD patients, as well as the levels of albumin, C-reactive protein (CRP) and interleukin-6 (IL-6). IL-6 serum levels were similar in patients with depression and patients without depression in the whole group, as in HD patients. In CAPD patients without depression IL-6 levels were significantly lower. CONCLUSIONS: The prevalence of depression was higher in HD comparing to CAPD patients. Although IL-6 level was higher in HD compared to CAPD patients, the relationship between depression and presence of inflammation parametars were observed in CAPD, but not in HD patients.

Spleen rupture associated with septic emboli and endocarditis in a hemodialysis patient.

We present an uremic patient on chronic hemodialysis with splenic septic emboli associated with active infective endocarditis and anaerobic bacteremia complicated by ruptured spleen. A 62-year-old female patient was admitted because of fever and pain in the left upper abdomen and swelling and hematoma around the left brachiocephalic arteriovenous fistula. Transthoracic echocardiography revealed mobile hyperechoic mass (vegetation) on the anterior mitral valve. Abdominal ultrasound scan showed multiple hypoechoic lesions of the enlarged spleen, described as possible necroses or abscesses, and computed tomography showed low-density inhomogeneous lesions in the enlarged spleen with large perisplenic hematoma, with spleen rupture. Blood culture revealed anaerobic Gram-negative bacilli ( Bacteroides spp.), ampicillin resistant. This is the first report of splenic rupture associated with anaerobic bacteremia and splenic septic emboli in a uremic patient on chronic hemodialysis. Splenic septic emboli with abscess/infarction in hemodialysis patients are a rare disorder but could be a consequence of dialysis access site infection and might predispose to splenic rupture. Ultrasound scan of abdomen is fast, inexpensive and easy to perform. As mortality is high, early surgical intervention on vascular access is mandatory.

Predictive factors of rebleeding and mortality following endoscopic hemostasis in bleeding peptic ulcers.

BACKGROUND/AIMS: To identify predictive factors of rebleeding and mortality after endoscopic therapy in patients with high risk peptic ulcers. METHODOLOGY: Patients hospitalized due to bleeding from high-risk peptic ulcers (Forrest classes Ia, Ib, IIa and IIb) during a five-year study, received endoscopic hemostatic therapy (diluted epinephrine injection, clipping or both) in addition to proton pump inhibitors. We looked for clinical, endoscopic and laboratory parameters that had influenced rebleeding and mortality in these patients. RESULTS: Among all patients (804) with peptic ulcer bleeding, 251 high-risk ulcer pateints received endoscopic hemostasis treatment. Thirty-four of them (13.5%) experienced in-hospital rebleeding. Majority of these achieved permanent hemostasis after second endoscopic treatment, while 14 (5.6%) needed surgery. Eighteen patients died (7.2%). Among parameters studied, severe anaemia, systolic and diastolic hypotension, shock presence, low Rockall score, ulcer size and time to hemostasis were factors which predicted rebleeding. Mortality predictive factors were: severe anaemia, hypotension, shock presence, lower Rockall and physical status scores, ulcer size and Forrest class. Conclusions: Early assesment of clinical and endoscopic predictive factors of rebleeding and mortality in patients with high-risk peptic ulcer bleeding could provide optimal therapeutical measures and follow-up. It could further reduce rebleeding and mortality rates in these patients.-16 months vs. 59.5 months, IQR=37.5-68.5 months, p<0.001) and the rate of death was lower (16.7% [2/12] vs. 83.3% [5/6], p=0.006). Logistic regression showed that a shorter duration of endoscopic interval increased the rate of resectability of gastric cancer (p<0.001) and a higher rate of unresectable gastric cancer and longer duration of endoscopic interval increased death (p=0.029 and p=0.004, respectively). CONCLUSIONS: After treatment of esophageal cancer, endoscopic examination at 12-month intervals is important to lower the rate of death due to metachronous gastric cancer.

Differences in epidermal thickness and expression of apoptosis regulatory proteins in the skin of patients with chronic renal failure and pruritus.

Chronic renal failure is often associated with skin itching (pruritus) in dialysis patients. In order to investigate the possible causes of pruritus, the epidermis of the thigh of 12 dialysis patients and 4 controls from patients without renal disease were examined. The sections of the epidermis were measured and immunohistochemically analyzed using antibodies to Bcl-2, Bax, caspase-3 proteins and TUNEL method. While the mean thickness of normal epidermis was 53 µm, in dialysis patients it ranged between 23 and 34 µm during the 3-5 year period on dialysis. Compared to normal skin, the fine balance between the Bcl-2 and Bax proteins did not greatly change in the epidermis of dialysis patients during the three years of dialysis. Following five-year dialysis, the epidermis displayed increased Bax and decreased Bcl-2 expression in the basal and intermediate epidermal layers, as well as the presence of apoptotic cells (TUNEL and caspase-3 positive) both in the superficial and intermediate epidermal layers. Our study demonstrated the predominant expression of cell death Bax proteins over cell survival Bcl-2 proteins, and apoptotic cells in the deeper layers of the epidermis in patients on long-term dialysis. We speculate that the thinning of the epidermis might be associated with the appearance of dead cells in the deeper epidermal layers, while the changed internal milieu of epidermal cells could possibly affect the intra-epidermal nerve endings thus leading to the sensation of pruritus.

Influence of local inflammation of the peritoneal membrane on diuresis and residual renal function in patients treated with peritoneal dialysis.

The aim of this study was to investigate the connection between local inflammation of the peritoneal membrane and diuresis, as well as the residual renal function (RRF) in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Twenty patients treated with CAPD participated in this cross-sectional study. To determine the influence of local inflammation of the peritoneal membrane, effluent interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels were measured. The level of IL-6, in the group as a whole, was significantly higher in effluent (7.87 pg/mL) than in serum (1.29 pg/mL). There was a significant correlation between effluent and serum IL-6 (r = 0.608; P = 0.002). There was also a significant relationship between effluent and serum IL-6 and duration of CAPD treatment, respectively (r = 0.577; P = 0.004; r = 0.528; P = 0.008). Further, there was a significant negative correlation between effluent IL-6 and daily diuresis (r = -0.533; P = 0.008), but there was no significant correlation between effluent IL-6 and RRF (r = -0.339, P = 0.072). On the other hand, the concentrations of effluent IL-6 were significantly higher in patients with RRF <2 mL/min than in those with RRF ≥2 mL/min (P = 0.039). In conclusion, local inflammation has a significant impact on the amount of diuresis and probably on RRF in patients on CAPD.

[Do we know all effects of heparins in hemodialyzed patients?]. / Znamo li sve o ucincima heparina u bolesnika lijecenih hemodijalizom?

Anticoagulation with heparins during hemodialysis (HD) is aimed at preventing the activation of coagulation in the extracorporeal circuit. As HD patients are exposed to unfractionated and low molecular weight heparins (LMWH) for years, non-hemorrhagic effects (osteoporosis, reduction of elevated blood pressure, with lesser intra- and interdialytic hypotensive episodes, effects on brain microvascular circulation and decreasing vascular dementia and Alzheimer's disease, and chronic and malignant diseases) require new trials with individualized doses of heparins.

Potential beneficial effects of low molecular weight heparin on cognitive impairment in elderly patients on haemodialysis.

Vascular cognitive impairment or mixed vascular cognitive impairment and Alzheimer's disease (AD) appear to be much more common in elderly patients than AD alone. Furthermore, vascular dementia (VaD) and AD are more prevalent in elderly patients receiving haemodialysis (HD), leading to a loss of independence and a poor quality of life. Hypotensive episodes in patients receiving HD contribute to vascular changes in the brain, with consequent progression of VaD and AD. The use of the lowest individually optimized bolus dose of low molecular weight heparin (LMWH) during HD, with fewer hypotensive episodes during and between HD procedures, may exert a sparing effect on changes in microvascular circulation and decrease the incidence of VaD and AD. We believe that long-term use of LMWH, with its direct effect on amyloid ß protein (Aß) in the blood and on Aß accumulation in the brain and indirect effects on prevention of complement activation, may delay the progression of cognitive impairment in patients receiving HD. There is a need for a robustly designed, prospective trial to evaluate the effects of long-term treatment with LMWH on mild cognitive impairment, VaD and AD in elderly patients receiving maintenance HD.

The influence of decreased low-molecular-weight heparin nadroparin dose on diastolic blood pressure in patients on hemodialysis.

The aim of present study was to assess the impact of decreasing single bolus dose of nadroparin on blood pressure in patients on hemodialysis (HD). Forty HD patients were included in this study. The bolus dose of nadroparin was decreased twice by 25%; this lower dose was maintained for last 4 weeks, during which the dose was adjusted. There were no significant differences between the first and the last predialysis: systolic blood pressure ([pre-SBP]; 131.05 ± 25.58 vs 125.92 ± 25.49 mm Hg; P = .133), diastolic blood pressure ([pre-DBP]; 73.82 ± 11.82 vs 72.89 ± 9.13 mm Hg; P = .653), and pulse pressure ([pre-PP]; 57.24 ± 20.39 vs 53.03 ± 21.20 mm Hg; P = .121). We found correlation between delta nadroparin and pre-DBP in the last HD (rho = 0.310; P = .031) but not between delta nadroparin and pre-SBP and pre-PP values. This is the first report of influence of nadroparin dose lowering on pre-DBP in HD patients.

The individually optimized bolus dose of nadroparin is safe and effective in diabetic and nondiabetic patients with bleeding risk on hemodialysis.

The risk of bleeding is a well-known complication in patients on hemodialysis (HD). The aim of this prospective study was to determine the lowest single bolus dose of low-molecular-weight heparin nadroparin for safe and effective HD in patients with a bleeding risk. Forty HD patients were divided into 4 subgroups with 10 participants (diabetics with and without a bleeding risk, nondiabetics with and without a bleeding risk). The actual starting bolus dose was decreased by 25% after the initial 4 weeks, further decreased by 25% of the starting dose after 4 weeks, and changed due to extracorporeal circuit clotting in the last 4 weeks. The parameters of coagulation were measured at the beginning, after 2 and 4 h of HD sessions. A significant reduction of nadroparin (first vs. last HD session) was observed in: diabetics with a bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P<0.001), diabetics without a bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P<0.001), and nondiabetics with a bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P<0.001). Altogether, the reduction of the nadroparin dose in these groups was 42.05%; 33.04%, and 46.19%, respectively. Although anti-Xa at hour 4 at the end of the study was <0.4 IU/mL in our diabetic and nondiabetic patients without a risk of bleeding, serious clottings in the extracorporeal circuit and vascular access thromboses were not found. This study demonstrated for the first time that individually optimized doses of nadroparin are sufficient for safe and effective HD in patients with a bleeding risk.