Slope of the estimated glomerular filtration rate and its associated factors among individuals with chronic kidney disease in the general Japanese population.

BACKGROUND: To suppress the incidence of end-stage kidney disease, we need to identify chronic kidney disease (CKD) patients with a high risk of rapid decline in the estimated glomerular filtration rate (eGFR). However, the current status of eGFR slope and its associated factors in the Japanese population have not been fully elucidated. METHODS: Among examinees aged 40-70 years in the 2014 Specific Health Checkup conducted by the National Health Insurance in Kobe, Japan (n = 61,985), we prospectively observed 7291 examinees with CKD stage G3 from 2014 to 2018. RESULTS: Until 2018, 4221 examinees continued to undergo annual SHCs for a total of five checkups per subject and had available records of all necessary data. The median eGFR change was -0.22 ml/min/1.73 m2/year. Only 9.2% of those subjects showed rapid eGFR decline (faster than -2.0 ml/min/1.73 m2/year). Logistic regression analysis identified diabetes, smoking habits, high urinary protein levels, older age, high systolic blood pressure, and low serum low-density lipoprotein cholesterol levels as independent predictors for rapid eGFR decline. Hemoglobin A1c levels did not contribute to the eGFR slope in CKD stage-G3 subjects with diabetes and proteinuria. CONCLUSION: Most Japanese CKD stage-G3 subjects had a very slow decline in eGFR. A small proportion of CKD individuals who have a predictive factor of rapid eGFR decline should receive considerable attention from a nephrologist.

Disruption of the glomerular basement membrane associated with nutcracker syndrome and double inferior vena cava in Noonan syndrome: a case report.

BACKGROUND: Nutcracker syndrome (NCS) is characterized by compression of the left renal vein (LRV) between the aorta and the superior mesenteric artery. While rare, NCS was reported to be accompanied by double inferior vena cava (IVC). We herein report a case of Noonan syndrome (NS) with double IVC who presented with macrohematuria and proteinuria. CASE PRESENTATION: The patient was a 23-year-old man, who had been diagnosed with NS due to RIT1 mutation, after showing foamy macrohematuria 3 weeks previously. A physical examination revealed low-set ears and a webbed neck. A urinalysis showed hematuria and proteinuria, and urinary sediments showed more than 100 isomorphic red blood cells per high-power field. His proteinuria and albuminuria concentrations were 7.1 and 4.5 g/g⋅Cr, respectively. Three-dimensional contrast-enhanced computed tomography (CT) showed double IVC and narrowing of the LRV after interflow of the left IVC. The aortomesenteric angle on a sagittal reconstruction of the CT image was 14.7°. Cystoscopy revealed a flow of macrohematuria from the left ureteral opening. On Doppler ultrasonography, there was scant evidence to raise the suspicion of the nutcracker phenomenon. Since severe albuminuria continued, a left kidney biopsy was performed. Light microscopy showed red blood cells in Bowman's space and the tubular lumen. Electron microscopy revealed disruption of the glomerular basement membrane (GBM). Vulnerability of the GBM was suspected and a genetic analysis revealed a heterozygous mutation at c.4793 T > G (p.L1598R) in the COL4A3 gene. Screening for coagulation disorders revealed the factor VIII and von Willebrand factor (vWF) values were low, at 47.6 and 23%, respectively. A multimer analysis of vWF showed a normal multimer pattern and he was diagnosed with von Willebrand disease type 1. As the bleeding tendency was mild, replacement of factor VIII was not performed. His macrohematuria and proteinuria improved gradually without treatment, and his urinalysis results have been normal for more than 6 months. CONCLUSIONS: The present case showed macrohematuria and proteinuria due to NCS in NS with double IVC and von Willebrand disease type 1. The macrohematuria and proteinuria originated from glomerular hemorrhage because of vulnerability of the GBM due to COL4A3 mutation.

Adipose-derived mesenchymal stem cells protects renal function in a rat model of emphysema.

BACKGROUND AND OBJECTIVE: The link between lung disease and kidney disorders has already been confirmed. Previous studies have documented that obstructive pulmonary disease is an independent predictor of decreased renal function, which reduces glomerular filtration rate. Recently, mesenchymal stem cells are the most important cell used in cell therapy. Accordingly, the present experiment was designed to evaluate the efficacy of adipose-derived mesenchymal stem cells (AMSCs) on improvement of renal function in elastase induced-pulmonary emphysema rats. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats divided into the 3 groups. Following intra-tracheal administration of elastase, the in vivo emphysema model established and confirmed according to the specific markers. Subsequently, systemic AMSCs injection was developed. the kidney injuries markers such as Blood urea nitrogen (BUN), creatinine, sodium and potassium as well as the kidney histopathologic parameters were assessed in all groups. Moreover, the oxidative stress markers levels including Malondialdehyde (MDA), Total antioxidant capacity (TAC), Catalase (CAT) and Glutathione peroxidase (GPx) were measured in kidney tissue and also inflammatory cytokines including IL-10, IL-6, and IFN-Ƴ were assessed in serum samples. RESULTS: The marked rise in kidney injuries markers were observed which showed by enhancement of BUN and Creatinine levels in emphysema rats compared to the control. Furthermore, the results demonstrated increases in MDA levels and decreases in antioxidant activity which was in line with increases in inflammation cytokines in renal tissue. Conversely, AMSCs treatment improved renal function as shown by the decreases BUN, Creatinine and proteinuria. Furthermore, renal histological assay demonstrate improvement in glomerular and tubular damage and inflammatory cells accumulation. CONCLUSIONS: Our results documented the promising kidney-protective properties of Adipose-Derived Mesenchymal Stem Cells in the kidney injuries induced by emphysema.

Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive Disease.

BACKGROUND: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs the potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as eGFR and proteinuria, is unclear. METHODS: We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables. RESULTS: At CKD stages 3-5, eGFR correlates reasonably well with the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1-2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis and IFTA, at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation, even at early disease stages. CONCLUSIONS: Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.

The association between frailty and chronic kidney disease; cross-sectional analysis of the Nambu Cohort Study.

BACKGROUND: Both frailty and chronic kidney disease (CKD) increase with age and share many similarities. Many studies have demonstrated an association between frailty and chronic kidney disease (CKD), but an association with dipstick proteinuria is limited. METHODS: This is the cross-sectional analysis of the Nambu Cohort Study at the beginning of observation. Frailty was diagnosed using Kihon Checklist. Logistic analysis was used to evaluate the association between frailty and CKD or dipstick proteinuria. RESULTS: Among a total of 630 outpatients [age, 78 (70-84) years, men, 50%], the prevalence of patients with pre-frailty and frailty was 32% and 40%, respectively. The proportion of patients with pre-frailty and frailty increased with decreasing estimated glomerular filtration rate (eGFR) and increasing dipstick proteinuria levels. The odds ratios (95% confidence intervals) for CKD stage of 60 < eGFR ≤ 45 ml/min/1.73 m2, and 45 ml/min/1.73 m2 < eGFR for frailty was 0.87 (0.56-1.35) and 2.54 (1.46-4.53), respectively, compared with non-CKD as a reference. Furthermore, the odds ratios for the frailty of dipstick proteinuria with ± and + or over were 1.36 (0.88-2.09) and 1.78 (1.00-3.17), respectively, when dipstick proteinuria-was used as a reference. Moreover, the combination of eGFR and dipstick proteinuria levels increased the odds ratio for pre-frailty and frailty. CONCLUSION: Elderly patients with CKD had a higher prevalence of pre-frailty and frailty. By adding urinary protein information to eGFR, the link between CKD and frailty becomes even more robust.

Iron deficiency in proteinuric children with nephrotic syndrome: A cross-sectional pilot study.

Massive proteinuria in nephrotic syndrome causes depletion of various proteins. Iron deficiency can occur due to urinary loss of iron, transferrin, and soluble transferrin receptors. We conducted this cross-sectional study of 52 children with proteinuric nephrotic syndrome, aged 1-12 years (mean 7.1±2.7 years). Hemoglobin (Hb), RBC indices (MCV, MCH, MCHC), percentage of hypochromic RBCs (Hypo-He), reticulocyte hemoglobin content (Ret-He), and serum ferritin were examined. Seven (13%) patients had iron deficiency anemia and another 10 (19%) exhibited iron deficiency. A higher proportion of children with steroid-resistant disease had anemia than did steroid-sensitive children (P=0.076). Thus, children with nephrotic syndrome may have iron deficiency (32.7%), which needs to be screened.

Pathophysiology of COVID-19-associated acute kidney injury.

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.

Preoperative proteinuria may be a risk factor for postoperative acute kidney injury：a meta-analysis.

OBJECTIVE: To investigate the relationship between preoperative proteinuria and postoperative acute kidney injury (AKI). METHODS: We performed a search on databases included PubMed, Embase, the Cochrane Library, and Web of Science, from December 2009 to September 2020. Data extracted from eligible studies were synthesized to calculate the odds ratio (OR) and 95% confidence interval (CI). A fixed or random effects model was applied to calculate the pooled OR based on heterogeneity through the included studies. RESULTS: This meta-analysis of 11 observational studies included 203,987 participants, of whom 21,621 patients suffered from postoperative AKI and 182,366 patients did not suffer from postoperative AKI. The combined results demonstrated that preoperative proteinuria is an independent risk factor for postoperative AKI (adjusted OR = 1.65, 95%CI:1.44-1.89, p < 0.001). Subgroup analysis showed that both preoperative mild proteinuria (adjusted OR = 1.30, 95%CI:1.24-1.36, p < 0.001) and preoperative heavy proteinuria (adjusted OR = 1.93, 95%CI:1.65-2.27, p < 0.001) were independent risk factors for postoperative AKI. The heterogeneity was combined because its values were lower. Further subgroup analysis found that preoperative proteinuria measured using dipstick was an independent risk factor for postoperative AKI (adjusted OR = 1.48, 95%CI:1.37-1.60, p < 0.001). Finally, preoperative proteinuria was an independent risk factor for postoperative AKI in the non-cardiac surgery group (adjusted OR = 2.06, 95%CI:1.31-3.24, p = 0.002) and cardiac surgery group (adjusted OR = 1.69, 95%CI:1.39-2.06, p < 0.001). CONCLUSION: Preoperative proteinuria is an independent risk factor for postoperative AKI and in instances when proteinuria is detected using dipsticks.

Organ-Specific Monitoring of Solitary Kidney after Living Donation by Using Markers of Glomerular Filtration Rate and Urinary Proteins.

BACKGROUND: Effective follow-up after living kidney donation is important for maintaining the renal function of the donor. We investigated whether the estimated glomerular filtration rate (eGFR) and urinary protein and enzyme levels can provide important information regarding the state of the remaining kidney after donor nephrectomy. METHODS: Seventy-five living donations were included (prospective/retrospective) in the study. The following parameters were measured up to 1 year after donor nephrectomy: serum creatinine and cystatin C as markers of the GFR; the high-molecular-weight urinary proteins as markers of glomerular injury; and the low-molecular-weight urinary proteins and urinary enzymes as markers of tubular function. RESULTS: One year after kidney donation, the creatinine and cystatin C values were 1.38-fold increased than their initial values, while the eGFR was 32% lower. At that time, 38% of donors had a moderate or high risk of CKD progression. The biochemical urinary glomerular and tubular kidney markers examined showed different behaviors. After a transient increase, the glomerular proteins normalized. Conversely, the detection of low-molecular-weight urinary proteins and enzymes reflected mild tubular damage at the end of the study period. CONCLUSIONS: Our findings suggest that for the evaluation of mild tubular damage, low-molecular-weight marker proteins should be included in the urine diagnostic of a personalized living kidney donor follow-up.

Associations Between Kidney Function, Proteinuria, and the Risk of Kidney Cancer: A Nationwide Cohort Study Involving 10 Million Participants.

Chronic kidney disease in its later stages is associated with increased risk of kidney cancer. We investigated whether chronic kidney disease at milder stages is associated with increased kidney cancer risk, using a retrospectively selected cohort of 9,809,317 adults in the Republic of Korea who participated in a nationwide health screening (2009-2016). We examined the impact of estimated glomerular filtration rate (eGFR), dipstick proteinuria, and interactive associations between the 2 factors on the risk of incident kidney cancer. During a median follow-up period of 7.3 years, 10,634 kidney cancers were identified. After adjustment for multiple confounders, participants with a reduced eGFR had an increased risk of kidney cancer (for eGFR <30 mL/minute/1.73 m2, adjusted hazard ratio = 1.18 (95% confidence interval: 1.01, 1.39); for eGFR 30-59 mL/minute/1.73 m2, adjusted hazard ratio = 1.22 (95% confidence interval: 1.14, 1.31)) compared with those with an eGFR of 60-89 mL/minute/1.73 m2. A dose-response relationship between the severity of proteinuria and incident kidney cancer was observed. Analyses of joint effects of eGFR and dipstick proteinuria showed that with the presence of proteinuria, kidney cancer incidence was markedly increased along with decreasing eGFR. Reduced eGFR and proteinuria are significantly associated with subsequent risk of kidney cancer, possibly in a synergistic manner.

Renal dysfunction in systemic sclerosis beyond scleroderma renal crisis.

Research regarding renal involvement in SSc has almost exclusively focused on scleroderma renal crisis (SRC). There are relatively limited data regarding renal impairment in SSc beyond SRC. We performed an electronic search using the key words systemic sclerosis or scleroderma combined with each of the following: renal dysfunction, kidney, glomerular filtration rate (GFR), proteinuria and hematuria. We searched for reports relevant to renal dysfunction in SSc beyond SRC. In 796 SSc patients recruited in five studies. 251 (31.5%) had GFR < 90 ml/min whereas 155(19.5%) patients had GFR < 60 ml/min. Most data indicate that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula should be considered as the most suitable tool for assessing renal function in SSc pts, since it provides similar results to measured GFR. These data indicate that renal dysfunction in SSc in not uncommon and therefore patients with SSc should have their renal function assessed by GFR estimation on a regular basis.

Lowest nocturnal systolic blood pressure is related to heavy proteinuria and outcomes in elderly patients with chronic kidney disease.

Ambulatory blood pressure monitoring (ABPM) can produce many variables, of which the lowest nocturnal systolic blood pressure (LNSBP) currently used in calculating morning surge is occasionally overlooked in recent kidney studies compared with other ABPM parameters. We explored the clinical effects of LNSBP in elderly patients with chronic kidney disease (CKD) in a multicenter, observational cohort study. A total of 356 elderly patients with CKD from 19 clinics were included in this analysis. We used multiple logistic regression and survival analyses to assess the associations between the lowest nocturnal systolic blood pressure and heavy proteinuria and kidney disease outcomes, respectively. The median age was 66 years, and 66.6% were men. The median eGFR was 49.2 ml/min/1.73 m2. Multivariate logistic regression analysis demonstrated that LNSBP (OR 1.24; 95% CI 1.10-1.39; P < 0.001; per 10 mmHg) was associated with heavy proteinuria. During the median follow-up of 23 months, 70 patients (19.7%) had a composite outcome; of these, 25 initiated dialysis, 25 had 40% eGFR loss, and 20 died. Cox analysis showed that the renal risk of LNSBP for CKD outcomes remained significant even after adjusting for background factors, including age, sex, medical history of hypertension and diabetes, smoking status, eGFR, 24-h proteinuria, and etiology of CKD (HR 1.18; 95% CI 1.06-1.32; P = 0.002; per 10 mmHg). Concentrating on LNSBP could be valuable in guiding antihypertensive treatment to control heavy proteinuria and improve renal prognosis in elderly CKD patients.

Proteinuric and nonproteinuric chronic kidney disease among patients with sickle cell anaemia (HbSS) attending a tertiary hospital in north-eastern Nigeria.

OBJECTIVE/BACKGROUND: Individuals with sickle cell anaemia (SCA) may manifest various forms of renal abnormalities. Proteinuria is an early marker of renal dysfunction and a strong risk factor for chronic kidney disease (CKD) progression in both patients with SCA and non-SCA population. Currently, the degree of attention given to proteinuric CKD far exceeds that of nonproteinuric CKD, and risk factors that might trigger a progressive decline of the glomerular filtration rate (GFR) in the absence of proteinuria have not been well evaluated in SCA. The aim of this study was to compare the clinical and laboratory parameters among SCA patients with proteinuric and nonproteinuric CKD. METHODS: This was a cross-sectional study conducted at the University of Maiduguri Teaching Hospital in north-eastern Nigeria between January 2013 and April 2018. Clinical variables including age of diagnosis of SCA, frequency of vaso-occlusive crises, number of hospitalizations per annum and transfusion therapy were collected. Laboratory data including haematological profile and renal function test were obtained from routine blood sampling. RESULTS: A total of 257 patients with SCA (HbSS) were enrolled during the study period of which 42 had proteinuric CKD, and 48 had nonproteinuric CKD. The two groups were matched for the number of hospital admission (p = .063) and blood transfusion per year (p = .450), frequency of painful crisis (p = .210), systolic blood pressure (p = .084) and diastolic blood pressure (p = .400). In the proteinuric CKD group, the mean serum creatinine was higher (332.17 µmol/L, p = .001) and the estimated GFR was lower (31.88 mL/min, p = .046). The serum alkaline phosphatase was higher in the nonproteinuric CKD group (81.81 IU/L, p = .012). CONCLUSION: Nonproteinuric CKD was more frequent than proteinuric CKD in our study population; however, the proteinuric group presented with more advanced disease.

Amyloid storm: acute kidney injury and massive proteinuria, rapidly progressing to end-stage kidney disease in AA amyloidosis of familial Mediterranean fever.

OBJECTIVE: Amyloid A nephropathy of FMF usually progresses over many years to end-stage renal disease (ESRD). We aim to describe an acute condition, termed here 'amyloid storm', typically manifesting with a rapid (≤2 weeks) increase in serum creatinine and urine protein, that has never been characterized in FMF amyloidosis. METHODS: This retrospective analysis features amyloid storm by comparing between FMF amyloidosis patients who have experienced an episode of amyloid storm (study group) and matched patients who have not (control group). The primary outcome was ESRD or death within 1 year from study entry. Featured data were retrieved from hospital files. RESULTS: The study and control groups, each comprising 20 patients, shared most baseline characteristics. However, they differed on the time from FMF onset to reaching serum creatinine of 1.2 mg/dl [26.5 years (s.d. 15.15) vs 41.55 (10.98), P = 0.001] and the time from the onset of proteinuria to study entry [8.8 years (s.d. 6.83) vs 15.75 (13.05), P = 0.04], culminating in younger age at study entry [39.95 years (s.d. 16.81) vs 48.9 (9.98), respectively, P = 0.05] and suggesting an accelerated progression of kidney disease in the study group. Within 1 year from study entry, 16 patients in the study and 3 in the control groups reached the primary endpoint (P = 0.000). The major triggers of amyloid storm were infections, occurring in 17 of 20 patients. CONCLUSION: Amyloid storm is a complication of FMF amyloidosis, induced by infection and associated with poor prognosis and death.

Metformin reduces proteinuria in spontaneously hypertensive rats by activating the HIF-2α-VEGF-A pathway.

Metformin has protective effects on diabetic nephropathy. However, the mechanism underlying the renoprotective action of metformin in spontaneously hypertensive rats (SHR) is not completely understood. We determined the role of metformin in proteinuria and investigated the mechanism. We measured the urinary protein concentration (mg/day) in 48-week-old SHR. Matched control animals were of the same genetic strain, Wistar-Kyoto (WKY). The rats received metformin (100 mg/kg/day) or vehicle for 10 months. Metformin improved renal function and reduced the proteinuria (urine protein: 48.4 ± 3.7 vs. 25.4 ± 1.8 mg, P < 0.01) induced by long-term high blood pressure. Metformin increased the production of vascular endothelial growth factor (VEGF)-A in rat kidneys and cultured rat podocytes. Metformin activated hypoxia-inducible factor-2α (Hif-2α) in response to VEGF but did not affect Hif-1α in rat kidneys and cultured rat podocytes. Metformin reduced the proteinuria induced by long-term high blood pressure in vivo and increased the VEGF-A production in rat kidneys and cultured rat podocytes, probably by activating the Hif-2α-VEGF signaling pathway. These findings provide a new mechanism for the renoprotective effects of metformin.

Clinical and pathological findings of SARS-CoV-2 infection and concurrent IgA nephropathy: a case report.

BACKGROUND: Since the Coronavirus Disease 2019 (COVID-19) outbreak, there is accumulating data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. Postmortem investigations reveal renal involvement in COVID-19, and most recently, several biopsy researches reveal that acute tubular injury, as well as glomerular nephropathy such as collapsing glomerulopathy were common histological findings. However, to our best knowledge, there is limited data regarding IgA nephropathy in the setting of COVID-19. CASE PRESENTATION: In the present case, we report a 65-year old Chinese woman who presented with dark-colored urine, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient's underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up. CONCLUSIONS: It is important to consider the underlying glomerular disease exacerbation as well as virus induced injury when dealing with renal abnormalities in patients with COVID-19. A kidney biopsy may be indicated to exclude a rapidly progressive glomerular disease.

Podocytopathies.

Podocytopathies are kidney diseases in which direct or indirect podocyte injury drives proteinuria or nephrotic syndrome. In children and young adults, genetic variants in >50 podocyte-expressed genes, syndromal non-podocyte-specific genes and phenocopies with other underlying genetic abnormalities cause podocytopathies associated with steroid-resistant nephrotic syndrome or severe proteinuria. A variety of genetic variants likely contribute to disease development. Among genes with non-Mendelian inheritance, variants in APOL1 have the largest effect size. In addition to genetic variants, environmental triggers such as immune-related, infection-related, toxic and haemodynamic factors and obesity are also important causes of podocyte injury and frequently combine to cause various degrees of proteinuria in children and adults. Typical manifestations on kidney biopsy are minimal change lesions and focal segmental glomerulosclerosis lesions. Standard treatment for primary podocytopathies manifesting with focal segmental glomerulosclerosis lesions includes glucocorticoids and other immunosuppressive drugs; individuals not responding with a resolution of proteinuria have a poor renal prognosis. Renin-angiotensin system antagonists help to control proteinuria and slow the progression of fibrosis. Symptomatic management may include the use of diuretics, statins, infection prophylaxis and anticoagulation. This Primer discusses a shift in paradigm from patient stratification based on kidney biopsy findings towards personalized management based on clinical, morphological and genetic data as well as pathophysiological understanding.

Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study.

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.

Melatonin attenuates hypertension and oxidative stress in a rat model of L-NAME-induced gestational hypertension.

Preeclampsia is a life-threatening multiorgan systemic disease with manifestations including gestational hypertension, oxidative stress, and vascular dysfunction. We aimed to evaluate the therapeutic effects of melatonin on an L-NAME (NLG-nitro-l-arginine methyl ester)-induced rat preeclampsia model. During gestation, L-NAME was added to drinking water at 50 mg/kg/day from gestation day (GD) 8. Rats received the combination of L-NAME with melatonin (10 mg/kg/day), or aspirin (1.5 mg/kg/day), and rats that received only L-NAME or no treatments were used as controls. Aspirin was mixed with rodent chow and melatonin was administered intraperitoneally. Blood pressure and urine protein content were monitored every 3 days. On GD19, blood samples were collected for biochemical analysis. Compared to untreated L-NAME rats, melatonin led to markedly lowered blood pressure and urine protein content, and recovery in the fetus alive ratio, fetal weight, and the fetal weight/placental weight ratio. Compared to untreated L-NAME rats, plasma antioxidant capacity and plasma malondialdehyde were increased and decreased by melatonin, respectively, in L-NAME rats. Melatonin treatment also reduced sFlt-1, increased PlGF, and decreased the sFlt-1/PlGF ratio. In the placenta, melatonin also reduced sFlt-1 levels and increased Nrf2, PlGF, and HO-1 levels. We have demonstrated in a rat model of preeclampsia that melatonin exerts significant protective effects through lowering blood pressure and reducing oxidative stress.

Case report: a Chinese girl with dent disease 1 and turner syndrome due to a hemizygous CLCN5 gene mutation and Isochromosome (Xq).

BACKGROUND: Female Dent disease 1 patients with low-molecular-weight proteinuria (LMWP) due to CLCN5 gene mutation were rarely reported, and these cases that the people were also with Turner syndrome (TS) were even hardly documented before. CASE PRESENTATION: Here we report a 3-year and 11-month old Chinese girl with short stature who had a karyotype of 46,X,i(X)(q10) and a de novo pathogenic variant in the CLCN5 gene on the short arm of X chromosome. Laboratory examinations showed that the patient had LMWP, hypercalciuria, hypophosphatemia, delayed bone age, and genital dysplasia. CONCLUSION: The combination of i(X)(q10) and CLCN5 mutation causes the deletion of the wild-type CLCN5 allele that results in Dent-1 and TS. To the best of our knowledge, this is the first case that a female CLCN5 mutation hemizygote is diagnosed with Dent-1 and Turner syndrome due to isochromosome X. Also, our case has indicated that the prevalence of the situation may be largely underestimated because of the mild signs of females with Dent-1.