Subclinical Renal Involvement Research Articles

Study protocol: a prospective single-center study for non-invasive biomonitoring of renal complications in cancer patients treated with immune checkpoint inhibitors.

The advent of immune checkpoint inhibitors (ICIs) has powerfully broadened the scope of treatment options for malignancies with an ongoing increase of indications, but immune-related adverse events (irAEs) represent a serious threat to treatment success. Agents directed against programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) are known to cause renal complications with an incidence of 3%. In contrast, subclinical renal involvement is estimated to be much higher, up to 29%. We recently reported about urinary flow cytometry-based detection of urinary PD-L1-positive (PD-L1+) kidney cells correlating with tubular PD-L1-positivity that reflected susceptibility to develop ICI-related nephrotoxicity as an irAE attending ICI treatment. Therefore, we designed a study protocol to evaluate urinary detection of PD-L1+ kidney cells as a tool for non-invasive biomonitoring of renal complications in cancer patients treated with ICIs. A prospective, controlled, non-interventional, longitudinal, single-center observational study will be conducted at the Department of Nephrology and Rheumatology of the University Medical Center Göttingen, Germany. We intend to enroll approximately 200 patients treated with immunotherapy from the Departments of Urology, Dermatology, and Hematology and Medical Oncology of the University Medical Center Göttingen, Germany. First, we will assess clinical, laboratory, histopathological, and urinary parameters in addition to urinary cell collection. Then, we will perform a correlative analysis between urinary flow cytometry of different PD-L1+ cell of renal origin with the onset of ICI-related nephrotoxicity. Because of growing ICI-treatment applicability with an expectable incidence of renal complications, providing cost-efficient and easily performable diagnostic tools for treatment-attendant and non-invasive biomonitoring becomes vital to improve both renal and overall survival rates in cancer patients receiving immunotherapy. https://www.drks.de, DRKS-ID DRKS00030999.

Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome.

Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the relationship between symptoms of long-COVID syndrome and serum levels of cystatin-c (CYSC), orosomucoid (ORM), l-arginine, symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). A total of 114 patients suffering from long-COVID syndrome were included in this observational cohort study. We found that serum CYSC was independently associated with the anti-spike immunoglobulin (S-Ig) serum level (OR: 5.377, 95% CI: 1.822-12.361; p = 0.02), while serum ORM (OR: 9.670 (95% CI: 1.34-9.93; p = 0.025) independently predicted fatigue in patients with long-COVID syndrome, both measured at baseline visit. Additionally, the serum CYSC concentrations measured at the baseline visit showed a positive correlation with the serum SDMA levels. The severity of abdominal and muscle pain indicated by patients at the baseline visit showed a negative correlation with the serum level of L-arginine. In summary, serum CYSC may indicate subclinical renal impairment, while serum ORM is associated with fatigue in long-COVID syndrome. The potential role of l-arginine in alleviating pain requires further studies.

POS-128 INFECTION-RELATED GLOMERULONEPHRITIS DUE TO SCRUB TYPHUS: A REPORT OF TWO CASES

Most patients with scrub typhus have some subclinical renal involvement, and symptomatic AKI has been observed in half of the cases. However, the literature has not reported infection-related glomerulonephritis (IRGN) due to scrub typhus.

IL33 and sST2 serum level in systemic sclerosis microvascular involvement.

Endothelial dysfunction and microvascular damage are hallmarks of systemic sclerosis (SSc). Objective of this study was to evaluate IL33 and ST2 serum levels in SSc patients and healthy controls (HC). Secondary aim was to evaluate the IL33 axis in the SSc microvascular manifestation. IL33 and sST2 have been assessed in 46 SSc patients and 24 HC matched for sex and age. Main clinimetric indexes were assessed. Skin perfusion of hands was evaluated by Laser Speckle Contrast Analysis (LASCA) and echocolordoppler ultrasound of renal arteries was performed to evaluate subclinical renal involvement. SSc patients had higher serum level of IL33 and sST2 than HC. IL33 and sST2 were significantly higher in SSc patient with digital ulcers (DUs) compared to SSc patients without DUs. SSc patients with late nailfold videocapillaroscopy (NVC) pattern had higher serum levels of sST2 than SSc patients with active NVC pattern. SSc patients without proximal-distal gradient (PDG) at LASCA had significantly higher sST2 serum level compared to SSc patients with PDG. SSc patients with renal resistive index (RRI)≥0.70 had higher serum levels of sST2 than SSc patients with RRI<0.70. A positive linear correlation was shown between sST2 and RRI, between sST2 and intrarenal S/D and between sST2 and PI. Kaplan-Meier curves show a significantly reduced free survival from DUs in patients with increased sST2 (p=0.025). In multivariate analysis, sST2 is associated with the development of new DUs. IL33 and sST2 are increased in SSc patients and ST2 might be a marker of microvascular damage.

Study of microalbuminuria in patients of rheumatoid arthritis and its correlation with erythrocyte sedimentation rate, C - reactive protein and rheumatoid factor

Background: Subclinical renal dysfunction and microalbuminuria are common in rheumatoid arthritis patients particularly with long standing disease and with severe disease activity. Despite the degree of interest shown in detection of microalbuminuria and its prognostic implications, the determinants of elevated urinary albumin excretion have not been studied well. This study was done to assess the subclinical renal involvement in Rheumatoid Arthritis (RA) patients.Methods: This cross-sectional study involving 50 patients attending attending the out-patient departments of Swaroop Rani Nehru Hospital, MLN Medical College, Prayagraj, U.P diagnosed with RA by modified ACR criteria (2010).Results: The mean age of the cases was 41.96 years (SD 10.80), of them 74% were females and 26% were males. MA was found in 15 patients (30%), of them. In MA positive group, mean ESR was 69.46±27.14, and CRP positive patients were 13 (86%), RA Factor positive patients were 12 (80%) and as compared to 31.28±5.03, 11 (32%), 14 (40%) respectively in MA negative group (p &lt;0.05 in all cases). Microalbuminuria was significantly correlated with ESR, CRP and RA factor (p value &lt;0.05).Conclusions: Presence of microalbuminuria indicates severe disease activity and long-standing rheumatoid arthritis. Microalbuminuria was found to be significantly correlated with disease activity in rheumatoid arthritis as assessed by ESR, CRP, RA Factor and anti CCP.

Renal involvement in primary Sjogren's syndrome: a prospective cohort study.

The objective of the study is to prospectively evaluate the spectrum of clinical and subclinical renal involvement in patients with primary Sjogren's syndrome (pSS). Of the 174 patients screened, seventy patients with pSS underwent renal function tests, urine examination, renal ultrasound, arterial blood gases, urine pH followed by urine acidification test and renal biopsy (if indicated). Renal tubular acidosis (RTA) was treated with alkali replacement and moderate-severe tubulointerstitial nephritis (TIN) was treated with oral prednisolone. Sixty-two patients completed 1-year follow-up. A comparison was made between patients with and without renal involvement. Thirty-five (50%) patients had renal involvement. They had a lower baseline eGFR (71.85 ± 18.04 vs. 83.8 ± 17, p = 0.005). Twenty-nine patients had RTA (25 complete and 4 incomplete). Eleven patients had urinary abnormalities. Patients with RTA (n = 29) were younger (34.9 ± 9 vs. 42 ± 11.3, p = 0.006), had fewer articular (34% vs. 78%, p = 0.001) and ocular sicca (62% vs. 88%, P = 0.01) than those without RTA (n = 41) and commonly presented with hypokalemic paralysis. On biopsy, TIN (9/17) and IgA nephropathy (3/17) were most common. On follow-up, there was no clinically significant change in eGFR; however, one patient with renal calculi and incomplete distal renal tubular acidosis (dRTA) progressed to complete dRTA. Two patients treated with steroids had marginal improvement in eGFR. Renal involvement in pSS is under-recognized with the most common manifestation being RTA presenting with hypokalemic paralysis. These patients are younger with less articular and sicca symptoms. Subclinical RTA may progress to complete RTA. Renal biopsy should be considered in all patients with renal involvement.

The Significance of Renal Functional Reserve in Еssential Hypertension

In the structure of causes of the end-stage chronic kidney disease is essential hypertension (EH) which takes the leading role. One of the pathogenic mechanisms of hypertensive nephropathy is a violation of intrarenal blood flow, which clinically manifesting with hyperfiltration. The objective: of the frequency of subclinical renal damage of patients with stage I EAH by water and salt loading and comparing these data with the standard criteria of essential nephropathy with hypertension. Patients and methods. The study involved 30 patients aged 27 to 59 years with diagnosed grade 1 essential hypertension who did not receive medical treatment and did not have the disease (lesions) of the kidneys. Mean albumin/creatin ratio of patients constituted 15,12±5,02 mg/g. According to the analysis of outpatient cards hypertension duration do not exceed during 5 years. All patients underwent 24-hour blood pressure monitoring and determining the method RFR water and salt load (under patent Ukraine 42,860) [9]. The results of daily monitoring of blood pressure (DMAT) were patients divided into two groups: the 1st group included patients who had been diagnosted the I step and I stage of EH, it comprised 22 patients (73.3%). Second group included patients who had been diagnosted the II stage of EH – 8 patients (26.7%). Results. Subclinical kidney damage were found in 8 patients (26.7%) in determining the method of water-salt load. (RFR 10±2,01% in 8 patients (26.7%) 1st group and RFR 22,31±3,9% in 22 patients (73.3%) significant difference between groups (p&lt;0.05). Among them, the state of hyperfiltration detected in 15 patients (50%) 281,55±40,66 ml/min per 1.73 m2. In eGFR 51,36±9,98 ml/min per 1.73 m2 had 6 people (20%), RFR was reduced and amounted to 11,02±6,65%. This shows that when increasing the blood pressure, kidney begins to lose its physiological reserve and its clinically possible to trace the transition state of hyperfiltration in decreased GFR. In determining GFR formula CKD-EPI reliable differences between groups were found. Conclusions. 1. Hypertension is an urgent problem and requires constant attention of the doctors of various specialties, complex problems that affect the incidence of kidney damage in the preclinical stage of hypertensive nephropathy. 2. The early hypertensive nephropathy criteria for the development of microalbuminuria may appear hyperfiltration and reduce renal functional reserve. 3. In EH patients with grade 1 hypertension, II stage, compared with patients with hypertension with I stage of kidney damage, were often observed and showed low RFR. 4. Using water-salt load for patients with EH and stages for the evaluation of kidney function can detect subclinical renal involvement, the development of microalbuminuria and reduced GFR.

Subclinical Kidney Damage in Hypertensive Patients: A Renal Window Opened on the Cardiovascular System. Focus on Microalbuminuria.

The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30mL/min/1.73m2 and 60mL/min/1.73m2 or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30-300mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30-300mg/g.There is clear evidence that urinary albumin excretion levels, even below the cut-off values used to define MAU, are associated with an increased risk of CV events. The relationships of MAU with a variety of risk factors, such as blood pressure, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced CV risk conferred by MAU. Nonetheless, several studies showed that the association between MAU and CV disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between MAU and CV risk remain to be elucidated. The simple search for MAU and in general of subclinical renal involvement in hypertensive patients may enable the clinician to better assess absolute CV risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard CV risk factors.

Interleukin-18 as a Biomarker of Subclinical Lupus Nephritis

Objectives: This study aims to investigate the relationship between serum interleukin-18 (IL-18) and its renal expression with histological classification of lupus nephritis in patients with insignificant proteinuria, and evaluate serum IL-18 as a biomarker of subclinical renal involvement in lupus patients. Patients and methods: Forty lupus patients (5 males, 35 females; mean age 26.3±7.9 years; range 16 to 52 years) with proteinuria less than 0.5 g/24 hours and 20 healthy controls (2 males, 18 females, mean age 25.5±6.3 years; range 16 to 49 years) were included. Patients underwent full history taking, thorough clinical examination, assessment of disease activity, measurement of serum IL-18, and renal biopsies for histopathological assessment and immunostaining for tissue expression of IL-18. Results: Lupus patients had significantly higher serum IL-18 levels than controls (612.4 and 209.3 pg/mL, respectively; p<0.01). Serum IL-18 was significantly higher in patients with classes III, IV and V lupus nephritis (609.1, 833.1 and 790 pg/mL, respectively) than in patients with class I and II (370 and 476.8 pg/mL, respectively). Immunostaining of IL-18 showed glomerular expression in classes IV and V, glomerular and tubular infiltration in class III, tubular pattern in class II and no staining in class I. Patients with diffuse glomerular IL-18 staining had higher levels of serum IL-18 than those with no staining (840.8 and 522.9 pg/mL, respectively; p=0.0). Those with diffuse tubular IL-18 staining had higher levels of serum IL-18 than those with no staining (514.2 and 393 pg/mL, respectively; p<0.05). Serum IL-18 correlated with serum creatinine and the activity index of renal biopsies. Conclusion: IL-18 may play a role in the pathogenesis of lupus nephritis. Results of this study showed that serum IL-18 reflects the extent of renal injury in lupus even in absence of significant proteinuria regardless of the level of disease activity; proposing its early role in pathogenesis of lupus nephritis. Thus serum IL-18 can be used as a biomarker that distinguishes the different histological classes of subclinical lupus nephritis.

Renal involvement in hypocomplementaemic urticarial vasculitis syndrome: a report of three paediatric cases

To describe the diagnosis and management of renal disease in three paediatric cases of hypocomplementaemic urticarial vasculitis syndrome (HUVS). Three children who were diagnosed with HUVS and developed abnormalities of renal function during the disease course are described. Urinary findings were heterogeneous: all the patients developed persistent microhaematuria, which was isolated in patient 1, associated with mild proteinuria in patient 2 and with nephrotic syndrome in patient 3. Renal biopsies were performed in all the patients: patients 1 and 2, who had normal levels of serum autoantibodies, shared a full-house IF (C3, C1q and Ig deposits), compatible with an SLE-like disease; patient 3 showed negative staining for IgG and IgM, but developed positive anti-dsDNA without fulfilling criteria for the diagnosis of SLE. Renal involvement in HUVS is probably more frequent and more severe than in adults and may appear later. Isolated microhaematuria can be the only sign of subclinical renal involvement: its role should not be underestimated and a renal biopsy should be considered. Previous observations of rapidly progressive nephritis and consequent end-stage renal disease in children suggest the need for prompt diagnosis and treatment of renal involvement.

Renal disease in scleroderma

Renal disease remains an important cause of morbidity and mortality in scleroderma. The spectrum of renal complications in systemic sclerosis includes scleroderma renal crisis (SRC), normotensive renal crisis, antineutrophil cytoplasmic antibodies-associated glomerulonephritis, penacillamine-associated renal disease, and reduced renal functional reserves manifested by proteinuria, microalbuminuria, or isolated reduction in glomerular filtration rate. The purpose of this review is to provide a concise and up-to-date review of the evaluation, risk stratification, pathogenesis, and management of scleroderma-associated renal disease. Although SRC survival has significantly improved, mortality of this complication remains high outside of specialized centers. Recent data demonstrate strong associations between anti-RNA polymerase III antibodies and SRC. Subclinical renal impairment affects approximately 50% of scleroderma patients and may be associated with other vascular manifestations. Subclinical renal involvement rarely progresses to end-stage renal failure; however, recent studies suggest it may predict mortality in patients with other vasculopathic manifestations. Testing for anti-RNA polymerase III antibodies should be incorporated into clinical care to identify patients at high risk for SRC. Recommendations from European League Against Rheumatism (EULAR), EULAR Scleroderma Trials and Research, and the Scleroderma Clinical Trials Consortium confirm angiotensin-converting enzyme inhibitors as first-line therapy for SRC, and give recommendations for second-line agents.

Renal disease in systemic sclerosis with normal serum creatinine

Prognosis of systemic sclerosis largely depends on involvement of internal organs. The aim was to evaluate renal impairment in patients with systemic sclerosis by measuring the Glomerular filteration rate (GFR) and then calculating the GFR using the Cockgroft and Gault formula and the Modification of Diet in Renal Disease Equation (MDRD) formula. Thirty one scleroderma patients were recruited from the Rheumatology and Rehabilitation Department, Cairo University Hospitals, mean age 43.25 +/- 11.28 years, 31 healthy controls were included. Disease severity was done using Medsger score. GFR was measured using classical Gates method TC99mDTPA. The modified Cockcroft and Gault formula and equation 7 from the MDRD were used for calculation of GFR. All patients had within normal serum creatinine levels. A normal GFR (>89ml/min) was found in 45.1%. Gates method showed reduced GFR was reported in 54.9%. Stage II chronic kidney disease (60-89 ml/min) found 32.3%, and stage III (30-59 ml/min) in 22.6%. The formulae used showed reduction of GFR in 35.29% of those affected by the Cockcroft-Gault and in 41.17% of those affected using the MDRD. No correlation to patients' age, disease duration, or severity. A positive correlation was also reported between the presence of renal involvement and pulmonary vascular involvement p = 0.04. Gates method showed reduction of the GFR in 54.9% of the systemic sclerosis patients. The formulae used were not as precise as the measured GFR in diagnosing all cases with subclinical renal involvement. Patients with systemic sclerosis should be screened for renal involvement irrespective of disease severity or duration.

Albuminuria in HIV-infected patients.

Albumin excretion, Analysis of urinary proteins by polyacrylamide gel electrophoresis (PAGE), and clinical evaluation were performed in 90 HIV-infected patients to assess subclinical renal involvement in HIV infection. Thirteen percent of all patients showed an albumin excretion > 20 mg/liter. Seven of four homosexual patients had albuminuria. Albuminuria occurred exclusively with T4 cell counts below 200/mm3. Polyacrylamide gel electrophoresis indicated glomerular lesions and showed no tubular proteinuria in patients with increased albumin excretion. It is concluded that subclinical renal involvement is not uncommon in HIV infection with T4 cell counts > 200/mm3. HIV-associated nephropathy and heroin-associated nephropathy may not be the main causes of renal involvement. In some cases, opportunistic viral infections may be the cause of microalbuminuria.