Current knowledge on histopathological changes occurring after COVID‐19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID‐19.
...Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID‐19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy.
Five patients were hospitalized for acute COVID‐19, and all were diagnosed with imaging‐confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip‐lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody‐mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells.
One patient died and one remained dialysis‐dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis.
In conclusion, diverse kidney pathology may be found in SARS‐CoV‐2–infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.
Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is ...considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 − 0.402 × age + 4.560 × 10sup.−3 × age2 − 2.621 × 10sup.−5 × age2 × MBP + 3.176 × 10sup.−3 × age × MBP − 1.832 × 10sup.−2 × MBP. MBP= (DBP) + 0.4(SBP − DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118–8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.
The most common cause of rapidly progressive glomerulonephritis in elderly, antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN), demands immunosuppressive therapy (IS) regimen ...in a multi-morbid disease burdened population. Our aim was to assess outcome differences in two age groups. The study included a total of 38 ANCA-GN renal limited patients (18 men) treated from 1990 to 2018, of which 11 were 65 years of age and older (median 70, min. - max. 66 - 79 years), and 27 younger than 65 (median 55, min. - max. 23 - 64 years). All patients were treated with mono/combination of IS. Most commonly applied IS in elderly was combination of IV cyclophosphamide and corticosteroids (CS) (in 9 81.8%), while in younger it was a combination of CS and cyclophosphamide or rituximab (59.2%). Older patients had comparable mortality (3, 14.8% vs. 4, 27.3%; P = 0.369), malignancies (1, 3.7% vs. 1, 9.1%; P = 0.5) and infectious complications (10, 46.7% vs. 7, 63.6%; P = 0.388). Ten patients at the end of the follow up were at renal replacement therapy (RRT), with no difference between age groups (6, 22.2% vs. 4, 36.4%; P = 0.369). Interestingly, from initial need for RRT, half of the younger and older patients recovered with IS. Our findings give more credit to the current paradigm to treat elderly ANCA-GN patients with IS therapy due to the similar outcome of elderly as younger ones. Key words: Antineutrophil Cytoplasmic antibodies, Glomerulonephritis, elderly, Immunosuppression, Mortality, Kidney failure
Objective: Aims of this study were to define thresholds for GH in a healthy low-risk European population using an age and gender-specific 95th percentile cut-offs, and to determine the prevalence of ...GH based on various eGFR equations across blood pressure (BP) categories. Design and method: In cross-sectional survey we included 1105 apparently healthy untreated participants from general population. There were 294, 412, and 400 normotensive, prehypertensive, and untreated hypertensive participants, respectively. The eGFR was calculated using CKD Epi equations, absolute GFR equation, MDRD and Cockcroft-Gault equations. Subjects were divided into the age quintiles. Prevalence of GF was determined for each equation and differences among BP categories were calculated. Results: Highest prevalence was found when GFR was estimated with CKD EPI equations. The lowest prevalence was observed with absolute GFR and Cockcroft-Gault equations (Figure 1). We failed to find differences in the prevalence of GH among the BP categories with the CKD EPI equations. Significant positive trend in the prevalence of GH from subjects with normal BP to the subjects with untreated hypertension was found when we used absolute GFR and Cockcroft-Gault equations. Subjects with GH had more obesity, dyslipidaemia, inflammation and salt intake compared to subjects with normal eGFR. In multinominal logistic regression, among subjects with eGFR >60 ml/min/1.73 m2, PP > 60 mmHg, ACR and salt intake increases the risk for GH by 96.4%, 90% and 83.9%, respectively. In the group of subjects with eGFR < 60 ml/min/1.73 m2, PP > 60 mmHg, ACR and being obese vs. having normal BMI increases the risk for GH by 94.4%, 88.8% and 10.2%, respectively. Obesity, ACR, PP and salt intake are risk factors for GH in apparently healthy Caucasians. Conclusions: There is no unique threshold value for GH, and age-gender - 95th cut off values should be used. CKD-Epi equations overestimate the prevalence of GH compared to de-indexed and Cockcroft-Gault equations. Differences in GH prevalence among BP categories were observed only without indexation for 1.73.
Abstract
Background and Aims
Distal renal tubular acidosis (dRTA) is a rare kidney disease. It can be inherited, i.e. primary (PdRTA), or acquired i.e. secondary (SdRTA). Secondary dRTA is more ...prevalent in the adult population and is usually caused by underlying autoimmune diseases (e.g. Sjogren syndrome). Both forms of dRTA are characterized by alkaline urine, kidney stone formation, nephrocalcinosis, chronic kidney disease, while metabolic acidosis can be variable. The treatment is based on the substitution of alkali substances. Our clinical study aims to describe a cohort of adult dRTA patients (both PdRTA and SdRTA) treated for 18 months by a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate, in terms of electrolyte disbalance correction, metabolic control, nephrolithiasis complications and kidney function.
Method
Data from seven patients with dRTA (3 with PdRTA and 4 with SdRTA, mean age 44 years, women 71%) taking prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in our center, were retrospectively collected and analyzed. The patients were previously treated with alkalizing agents (mostly sodium bicarbonate and potassium citrate). Patients were followed up for up to 18 months after inducing prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate was introduced. Kidney function, metabolic acidosis control (serum bicarbonate), serum electrolytes, urinary calcium excretion, and urinary citrate were measured. Nephrolithiasis complications and patient compliance were also evaluated. The urine and blood samples were analyzed two weeks after introducing the new drug and every 3 months afterward. Data are presented as mean ± standard error of the mean. Student T-test was used to calculate p values.
Results
The patients were taking on average 48 mEq of the drug (range 32-72 mEq), the dosage remained the same during the follow-up period (p = 0.365). The average follow-up period was 10 months (range 3-18 months). The metabolic acidosis was well controlled (serum bicarbonate was 24 ± 1.71 mmol/l at baseline, 24.4 ± 1.5 mmol/l at the end of follow-up, p = 0.680). Kidney function remained stable (GFR 73.5 ± 22.67 ml/min/1.73 m2 at baseline, 73 ± 22.69 ml/min/1.73 m2 at the end, p = 0.977). Serum potassium was also well controlled (4.07 ± 0.45 mmol/l at baseline, 4.32 ± 0.40 mmol/l at the end, p = 0.344), as well as calcium in 24-hour urine (2.75 ± 0.59 mmol/24-hour urine at baseline, 2.35 ± 0.12 mmol/24-hour urine at the end, p = 0.222). Urinary citrate levels (calculated as citrate/creatinine ratio) remained in the lower part of the reference range during the follow-up period (103.3 ± 68.3 mmol/mol at baseline, 114.6 ± 64.9 mmol/l at the end, p = 0.775). Two patients had acute renal colic caused by nephrolithiasis, without the need for surgical intervention. Safety and adherence to treatment remained good with no gastrointestinal side effects, one patient discontinued the drug due to headaches.
Conclusion
Our data show that treatment with a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in adult dRTA patients can achieve good control of metabolic acidosis and electrolyte disbalance with stable kidney function without the need to escalate the dose of the drug during the follow-up period. The adherence to the treatment remained good with no gastrointestinal side effects.
Objective: High blood pressure (BP) is an independent risk factor for cardiovascular (CV) disease. The current ESH guidelines consider normal BP from 120-129/80-84 mmHg, and high-normal BP ...130-139/85-89 mmHg. Metabolic profile, kidney function, and other risk factors determine the global CV risk which is important for proper treatment tailoring. We aimed to analyze the metabolic profile, white blood cell (WBC) count and high-sensitive C-reactive protein (hs-CRP), albuminuria (ACR), as well as endothelial damage marker; hepatocyte growth factor (HGF) in subjects with optimal BP, normal, and high-normal BP. Design and method: Data from 612 subjects (a random sample of adult rural population included in the ENAH study; 58% women, average age 41±14 years) were analyzed. Fasting blood and urine samples were collected. BP was measured using oscillometric device according to the ESH guidelines. Subjects were divided into two groups: OBP (optimal BP<120/80 mmHg, N=295), NHN (normal BP - normal and high-normal BP 120/80-140/90 mmHg, N=317). Results: Subjects in NHN group are older than subjects in OBP group (p<0.001). A significantly higher number of subjects with metabolic syndrome were observed in the NHN group (p < 0.001). There was no difference in inflammatory markers (WBC, hs-CRP) between groups. Albuminuria (ACR) was not higher in the NHN group. We found a positive correlation of HGF concentration and BP only in the NHN group. At the end of 7-years-follow up period 12.6% and 48.2% developed AH in the OBP and the NHN group, respectively (p< 0.001). The average annual incidence of AH for subjects with OBP was 2%, and for NHN subjects was 8%. Conclusions: Metabolic disturbances are significantly more frequent in subjects with NHN compared with those with OBP. In addition, in this group, we found a positive correlation between endothelial damage and BP. There is a higher incidence of new-onset AH in NHN the group during the follow-up period. Lifestyle changes should be implemented in all subjects with NHN BP aiming to reduce the risk of developing sustained AH, and drug therapy should be considered particularly in those with other risk factors.
Objective: The serum uric acid (SUA) has an important role in the pathogenesis of hypertension, and it is associated with risk for cardiovascular (CV) morbidity and mortality. There is no consensus ...for treatment of asymptomatic SUA. The aim of our study was to investigate prevalence and predictors for asymptomatic hyperuricemia in general rural adult population (ENAH rural study). Design and method: In this cross-sectional survey we included 773 from the original ENAH cohort (men 34.8%, average age 59 ys) who completed structured questionnaire, were clinically examined, fasting blood was drawn and urine samples were collected. Blood pressure (BP) was measurement according to the ESH guidelines. Subjects were divided into 4 groups: treated controlled hypertensives (TCHT 25.4%), treated uncontrolled hypertensives (TUHT 24.9%), untreated hypertensives (UTHT 14.2%) and untreated normotensives (UTNT 35.3%). Thresholds values for hyperuricemia were defined as >333 umol/L for men and >300 umol/L for women. Results: The prevalence of hyperuricemia was 45.5%. It was more common in men, subjects with eGFR CKD EPI < 60 ml/min/1.73 m2, TCHT/TUHT, those with uricostatics, and diuretic therapy (52%, p<0.001; 18%, p<0.001; 68%, p<0.001; 11%, p=0.01; 6%, p=0.002, respectively). Subjects with hyperuricemia were older, had higher values of BP and lower eGFR CKD Epi (p<0.001 for all). In bivariate logistic regression, age, male gender, SBP/DBP, hypertensive status (TUHT>TCHT>UNHT), and diuretic therapy increase, while antihypertensive therapy and eGFR CKD Epi >60 ml/min/1.73 m2 decrease the risk for hyperuricemia. With the progression of CKD, risk for hyperuricemia increases, starting from CKD G2 (p<0.001). In multivariate logistic regression, only male gender, and hypertensive status (TCHT >TUHT> UNHT) increase the odds for hyperuricemia, TCHT {OR 4.69, 95% CI (2.98 – 7.40), p<0.001} and TUHT {OR 4.37, 95%CI (2.7-6.82), p<0.001} being the most predictive. Conclusions: The prevalence of asymptomatic hyperuricemia in rural population is very high. Male gender and hypertensive status independently increase the risk for hyperuricemia in Croatian rural population.
Abstract
Background and Aims
Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome in adult population. Our aim was to assess long term renal outcome of primary membranous ...nephropathy patients.
Method
In this retrospective study adult patients with biopsy proven membranous nephropathy from 2000 till 2015 with follow up of at least 5 years from UHC Zagreb were included. Extensive clinical workup was done to exclude patients with secondary MN. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels.
Results
Between 2000 and 2015, 48 patients were diagnosed to have idiopathic/primary membranous nephropathy, out of which 33 (68%) MN patients had follow up of at least 5 years and where further analyzed. They were predominantly male 20 (60.6%) of average age of 52 years (min – max 19 - 76). High risk MN patient 25 (75%) were treated with immunosuppressive therapy, dominantly with cyclophosphamide and corticosteroids. During the median follow up of 10 (7 – 14) years, 19 (57%) accomplished complete remission and 11 (33%) partial remission. One (3%) patient did not achieve remission and 2 (6.1%) were in relapse of nephrotic syndrome at last follow up. Proteinuria significantly decreased (6.2 (3.3 – 10.9) vs. 0.2 (0.14 – 0,90); p < 0.001) and there was no significant change in creatinine level (87 (42.8 – 101.5) vs. 93 (68.5 – 140.5; p = 0.332)). In follow up there were 5 (15%) carcinomas detected; one of each origin (colon, pancreas, lung, prostate, lymph nodes) approximately 7,8 years after the diagnose of MN. Limitation of this study could be selection bias but there was no difference in renal function at presentation of all MN patients and those who had at least 5 years follow up.
Conclusion
Renal long-term outcome of patients with idiopathic MN in our cohort was excellent. Nevertheless, there is high prevalence of cancer and therefore regular screening for cancer disease should take place in this population of patients. Also, drugs with cancerogenic potential should be avoided, as well as bear in mind cumulative dose of drugs applied.
Abstract
Background and Aims
Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim ...was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol.
Method
In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels.
Results
During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease.
Conclusion
Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.
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