Related Kidney Disease Research Articles

Application of Plato analysis method in identifying the security risks of the clinical cases

Objective To apply Plato analysis method to clinical cases which were reported from clinical nursing, finding out the key link of the risks which were related to the cases: the key age, the key period, the key spectrum of disease and the key projects, etc. To carry out the feedforward control of the quality of care, and ensure the quality and safety of nursing. Methods A database were set up including clinical special cases, high-risk cases, security hidden danger cases and emergency cases. The two eight principle of Plato analysis method was used to find out the main factors, the principal contradiction, the key hazard and the key problems of the cases, etc. The aim was to provide guidelines of risk analysis, risk prevention and risk aversion for nurses, and improve their consciousness of security hidden danger, and reduce security hidden danger cases. Results The results of 207 cases collected from 2014 to 2015 showed that the main risks involved the age groups were 41-80 years old and 21-30 years old. The major risks involved the spectrum of disease were the nervous system, cardiovascular disease, surgical anesthesia related problems, kidney disease, cancer and respiratory system. The major risks involved the time were the midnight, morning and afternoon. The major risks involved the locations were sickroom, emergency room, auxiliary inspection departments and outpatient. The major risks involved items were disease mutation, psychological problems, medication safety and instrument safety, among the disease mutation, timely discovered, rescued 13 patients with heart and breathing pause, stop 13 patients who attempted suicide. Since the Plato analysis method was applied to identify the security risks of the clinical cases, the number of falling, all kinds of pipe shed, skin problems and suicides were decreased from 6, 6, 7, 5 in 2014 to 2, 2, 2, 1 in 2015, declining trend year by year. Conclusions Applying the Plato analysis method to identify the security risks of the clinical cases which can find out the main problems of cases and improve nursing quality and management efficiency. Key words: Plato; Case; Risk; Identify

Effects of hydro-alcoholic extract of Vitex agnus-castus fruit on kidney of D-galactose-induced aging model in female mice.

The aim of the present study was to evaluate the effect of a hydro-alcoholic extract of Vitex agnus-castus (VAC) fruit on blood urea nitrogen (BUN), creatinine (Cr) and, kidney histology of a female mouse model of D-galactose induced aging. In this experimental study, 72 NMRI mice were divided into 6 groups: control, VAC, D-galactose, D-galactose+VAC, aging, and aging+VAC. D-galactose was injected for 45 days and, VAC extract administered in the last 7 days, twice a day. Serum BUN and Cr levels were not significantly changed in the D-galactose and natural aged animals in comparison to control group. Histological changes such as nuclear pyknosis, proximal cell swelling, infiltration of inflammatory cells, tubular dilatation and, vasodilatation were observed in both D-galactose and natural aged mice. Further, glomerules diameter was decreased in them. Administration of VAC could attenuate the histological alterations. These results indicate that VAC may have beneficial effects on aging and aging related kidney disease.

New Pharmacologic Agents That Target Inflammation and Fibrosis in Nonalcoholic Steatohepatitis-Related Kidney Disease.

Epidemiologic data show an association between the prevalence and severity of nonalcoholic fatty liver disease and the incidence and stage of chronic kidney disease (CKD); furthermore, nonalcoholic steatohepatitis (NASH)-related cirrhosis has a higher risk of renal failure, a greater necessity for simultaneous liver-kidney transplantation, and a poorer renal outcome than cirrhosis of other etiologies even after simultaneous liver-kidney transplantation. These data suggest that NASH and CKD share common proinflammatory and profibrotic mechanisms of progression, which are targeted incompletely by current treatments. We reviewed therapeutic approaches to late preclinical/early clinical stage of development in NASH and/or CKD, focusing on anti-inflammatory and antifibrotic treatments, which could slow the progression of both disease conditions. Renin inhibitors and angiotensin-converting enzyme-2 activators are new renin-angiotensin axis modulators that showed incremental advantages over angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers in preclinical models. Novel, potent, and selective agonists of peroxisome proliferator-activated receptors and of farnesoid X receptor, designed to overcome limitations of older compounds, showed promising results in clinical trials. Epigenetics, heat stress response, and common effectors of redox regulation also were subjected to intensive research, and the gut was targeted by several approaches, including synbiotics, antilipopolysaccharide antibodies, Toll-like receptor-4 antagonists, incretin mimetics, and fibroblast growth factor 19 analogs. Promising anti-inflammatory therapies include inhibitors of NOD-like receptor family, pyrin domain containing 3 inflammasome, of nuclear factor-κB, and of vascular adhesion protein-1, chemokine antagonists, and solithromycin, and approaches targeting common profibrogenic pathways operating in the liver and the kidney include galectin-3 antagonists, and inhibitors of rho-associated protein kinase and of epidermal growth factor activation. The evidence, merits, and limitations of each approach for the treatment of NASH and CKD are discussed.

Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation.

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation.

The 14th Ile residue is essential for Leptin function in regulating energy homeostasis in rat.

LEPTIN (LEP) is a circulating hormone released primarily from white adipocytes and is crucial for regulating satiety and energy homeostasis in humans and animals. Using the CRISPR technology, we created a set of Lep mutant rats that carry either null mutations or a deletion of the 14th Ile (LEP∆I14) in the mature LEP protein. We examined the potential off-target sites (OTS) by whole-genome high-throughput sequencing and/or Sanger-sequencing analysis and found no OTS in mutant rats. Mature LEP∆I14 is incessantly produced and released to blood at a much elevated level due to the feedback loop. Structure modeling of binding conformation between mutant LEP∆I14 and LEPTIN receptor (LEPR) suggests that the conformation of LEP∆I14 impairs its binding with LEPR, consistent with its inability to activate STAT3-binding element in the luciferase reporter assay. Phenotypic study demonstrated that Lep∆I14 rats recapitulate phenotypes of Lep-null mutant rats including obesity, hyperinsulinemia, hepatic steatosis, nephropathy, and infertility. Compared to the existing ob/ob mouse models, this Lep∆I14/∆I14 rat strain provides a robust tool for further dissecting the roles of LEP in the diabetes related kidney disease and reproduction problem, beyond its well established function in regulating energy homeostasis.

A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats.

Aside from kidney transplantation - a procedure which is exceedingly dependent on donor-match and availability leading to excessive costs - there are currently no permanent treatments available which reverse kidney injury and failure. However, kidney-specific targeted gene therapy has outstanding potential to treat kidney-related dysfunction. Herein we report a novel kidney-specific targeted gene delivery system developed through the conjugation of chitobionic acid (CBA) to a polysorbitol gene transporter (PSGT) synthesized from sorbitol diacrylate and low molecular weight polyethylenimine (PEI) carrying hepatocyte growth factor (HGF) gene to alleviate unilateral ureteral obstruction (UUO) in rats. CBA-PSGT performed exceptionally well for targeted delivery of HGF to kidney tissues compared to its non-targeted counterparts (P<0.001) after systemic tail-vein injection and significantly reduced the UUO symptoms, returning the UUO rats to a normal health status. The kidney-targeted CBA-PSGT-delivered HGF also strikingly reduced various pathologic and molecular markers invivo such as the level of collagens (type I and II), blood urea nitrogen (BUN), creatinine, and the expressions of ICAM-1, TIMP-1 and α-SMA which play a critical role in obstructive kidney functions. Therefore, CBA-PSGT should be further investigated because of its potential to alleviate UUO and kidney-related diseases using high affinity kidney targeting.

A Case of Chronic Interstitial Nephritis From IgG4 Related Kidney Disease

A Case of Chronic Interstitial Nephritis From IgG4 Related Kidney Disease

Cystatin C provides a better estimate of the effect of glomerular filtration rate on serum human epididymis protein 4 concentrations.

We evaluated the effect of kidney glomerular function on serum concentrations of human epididymis protein 4 (HE4) using creatinine (Cr), cystatin C (CysC) and related chronic kidney disease epidemiology collaboration (CKD-EPI) equations. We enrolled 101 women aged ≤56 years with a glomerular filtration rate (GFR) (estimated by CKD-EPI eGFRCr) ranging from 60 to 120 mL/min/1.73 m2, free of any disease and biological and life-style factors known to influence serum HE4 concentrations, and we measured serum Cr, CysC and HE4 concentrations. Cr and CysC values were included in the three CKD-EPI equations to obtain GFR estimates. A statistically significant increase in HE4 median concentrations was detected in subjects with an eGFRCr between 60 and 74 mL/min/1.73 m2 when compared with those with an eGFR >90 mL/min/1.73 m2 (54.2 vs. 42.2 pmol/L, p=0.003). Regression models showed that CysC measurement per se and eGFRCysC were the most sensitive markers to catch HE4 increases due to a mild decrease in renal function [adjusted r2, 0.38 (p=0.00003) and 0.37 (p=0.0004), respectively]. By assuming baseline CysC and eGFRCysC at 0.80 mg/L and 101.5 mL/min/1.73 m2, an increase of 0.10 mg/L in CysC concentrations and a decrease of 10 mL/min of eGFRCysC implied an average (±SE) increase in serum HE4 concentrations of 9.2 (±1.2) and 8.8 (±1.1) pmol/L, respectively. Our study shows that a better estimate of the effect of GFR on serum HE4 is obtained by measuring CysC in serum or using CKD-EPI eGFRCysC equation.

Association between serum uric acid related genetic loci and diabetic kidney disease in the Chinese type 2 diabetes patients

AimWe aimed to investigate the association between uric acid related genetic loci and DKD susceptibility in type 2 diabetes patients. MethodsSeventeen single nucleotide polymorphisms (SNPs) from thirteen loci related to serum uric acid were genotyped in 2,892 type 2 diabetes patients. Associations between SNPs and uric acid, SNPs and quantitative traits related to DKD or its susceptibility were evaluated. ResultsIn this study, uric acid showed a strong association with DKD (OR=1.006, p<0.0001). GCKR rs780094, SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142, SLC22A12 rs505802 and NRXN2 rs506338 were positively associated with serum uric acid (p=3.79E-05, 0.0002, 2.04E-10, 2.23E-09, 0.0018 and 0.0015, respectively). SLC2A9 rs11722228 and SF1 rs606458 were significantly associated with DKD (OR=0.864, p=0.0440; OR=1.223, p=0.0038). SLC2A9 rs3775948 and ABCG2 rs2231142 were associated with DKD marginally (OR=0.878, p=0.0506; OR=0.879, p=0.0698). SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 and SF1 rs606458 were significantly associated with the estimated glomerular filtration rate (p=0.0005, 0.0006, 0.0003, and 0.0424, respectively). ConclusionsOur study indicated that the uric acid related alleles of SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 might affect DKD susceptibility and possibly through non-uric acid pathway in the Chinese people with type 2 diabetes.

Ultrasonography of the Kidney: A Pictorial Review.

Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most pathological changes in the kidneys are distinguishable with ultrasound. In this pictorial review, the most common findings in renal ultrasound are highlighted.

Response Adapted Induction Therapy for Multiple Myeloma

Background: Bortezomib (bort), lenalidomide (len), cyclophosphamide (cy), and dexamethasone (dex) combinations are acceptable initial treatment options for multiple myeloma (MM). At least 2 of these agents are generally used in initial treatment. Continuous len /dex treatment in older patients (pts) may be superior to shorter courses of 3 drug therapy (Benboubker L et al. N Engl J Med 2014; 371:906-917). Standardized treatment programs for cancer pts are important in a changing healthcare reimbursement system. Response adapted therapy for multiple myeloma has the potential to reduce toxicity, limit multi-drug resistant subclone development thus improving survival, and provide cost savings.Methods: The Cleveland Clinic multiple myeloma carepath initiates 2 drug response adapted therapy with len/dex (bort/dex if there is evidence of myeloma related kidney disease or unacceptable len cost to pt). This is an update to preliminary data of Narkhede et al 2014 ASH abstract 2620. Response assessment per current IMWG criteria is obtained with each cycle of therapy, although bone marrow biopsy is not required to confirm complete response. Pts with progressive disease (PD) after one cycle or lack of partial response (PR) after 2 cycles have either bort or len added to the initial 2 drug therapy. If needed, sequential addition of cy and liposomal doxorubicin occurs until at least PR is obtained. Pts achieving PR after 2 cycles are continued on 2 drug therapy. All transplant eligible pts are offered high dose melphalan and autologous stem cell transplant if they achieve PR followed by maintenance therapy. Pts not eligible for transplant are continued on effective therapy for up to 3 years as tolerated. Supportive care with bisphosphonates, vaccinations, zoster prophylaxis, and thromboembolism prophylaxis are outlined in this carepath.Results: From October 2012 to March 2015 carepath therapy was used in 53 pts not eligible for or unwilling to participate in clinical trials. Outcome data was attained through July 31, 2015 and median follow up was 16 months. 10 pts are off carepath treatment due to death (n=4), drug induced anorexia (n=1), or disease progression (n=5). 5 of these 10 pts were treated with ≥ 3 drugs. 3 of the 4 deaths occurred in pts high risk by FISH or MyPRS analysis. For all pts, response rates of VGPR or better were 55% in pts treated with 2 drugs and 41% in pts treated with ≥ 3 drugs. Of the 43 pts remaining on carepath based therapy, 26 pts have required only 2 drugs during the induction phase of treatment with 58% achieving at least very good partial response (VGPR) prior to either transplant or consolidation maintenance therapy. 17 pts required 3 or more drugs during the induction phase with 35% achieving at least VGPR prior to transplant or consolidation maintenance. Grade 3 or higher toxicity included hyperglycemia (n=4) due to dex, neutropenia (n=4) due to len, febrile neutropenia (n=2) due to len, insomnia (n=2) due to dex, and upper respiratory infection (n=2). One episode each of acute coronary syndrome due to dex (pt not on len), pancreatitis due to dex, anorexia due to len, sensory peripheral neuropathy due to bort, and tumor lysis syndrome due to len/dex occurred.Conclusion: Response adapted carepath based therapy provides effective disease control for the majority of MM pts treated while limiting cost due to the lower utilization of 3 drug therapy. While overall survival data is immature, the primary goal of response adapted therapy is to improve overall survival of MM pts by limiting early development of multi-drug resistant subclones. 55% of our pts required only 2 drug induction therapy to achieve a VGPR or better and 84% of these patients remain on carepath based therapy. Estimated cost savings on drug alone is over $4000 per cycle in the 2 drug treated pts. Cost savings may be underestimated as 73% of pts received len/dex as induction therapy and thus incurring less infusion related cost. DisclosuresValent:Takeda/Millennium: Speakers Bureau; Celgene: Speakers Bureau. Off Label Use: cyclophosphamide for the treatment of multiple myeloma. Faiman:Amgen/Onyx: Consultancy; Celgene: Consultancy, Speakers Bureau; Takeda/Millennium: Consultancy. Hamilton:Takeda/Millennium: Speakers Bureau. Smith:celegene, spectrum, genentech: Honoraria. Reu:Takeda/Millennium: Research Funding; Novartis: Research Funding; Celgene: Research Funding.

Targeting Rapamycin to Podocytes Using a Vascular Cell Adhesion Molecule-1 (VCAM-1)-Harnessed SAINT-Based Lipid Carrier System.

Together with mesangial cells, glomerular endothelial cells and the basement membrane, podocytes constitute the glomerular filtration barrier (GFB) of the kidney. Podocytes play a pivotal role in the progression of various kidney-related diseases such as glomerular sclerosis and glomerulonephritis that finally lead to chronic end-stage renal disease. During podocytopathies, the slit-diaphragm connecting the adjacent podocytes are detached leading to severe loss of proteins in the urine. The pathophysiology of podocytopathies makes podocytes a potential and challenging target for nanomedicine development, though there is a lack of known molecular targets for cell selective drug delivery. To identify VCAM-1 as a cell-surface receptor that is suitable for binding and internalization of nanomedicine carrier systems by podocytes, we investigated its expression in the immortalized podocyte cell lines AB8/13 and MPC-5, and in primary podocytes. Gene and protein expression analyses revealed that VCAM-1 expression is increased by podocytes upon TNFα-activation for up to 24 h. This was paralleled by anti-VCAM-1 antibody binding to the TNFα-activated cells, which can be employed as a ligand to facilitate the uptake of nanocarriers under inflammatory conditions. Hence, we next explored the possibilities of using VCAM-1 as a cell-surface receptor to deliver the potent immunosuppressant rapamycin to TNFα-activated podocytes using the lipid-based nanocarrier system Saint-O-Somes. Anti-VCAM-1-rapamycin-SAINT-O-Somes more effectively inhibited the cell migration of AB8/13 cells than free rapamycin and non-targeted rapamycin-SAINT-O-Somes indicating the potential of VCAM-1 targeted drug delivery to podocytes.

Diet-induced obesity and kidney disease – In search of a susceptible mouse model

Obesity and metabolic syndrome are independent risk factors for chronic kidney disease, even without diabetes or hyperglycemia. Here, we compare two mouse models that are susceptible to diet-induced obesity: the relatively renal injury resistant C57BL/6J strain and the DBA2/J strain which is more sensitive to renal injury. Our studies focused on characterizing the effects of high fat diet feeding on renal oxidative stress, albuminuria, fibrosis and podocyte loss/insulin resistance. While the C57BL/6J strain does not develop significant pathological changes in the kidney, at least on lard based diets within the time frame investigated, it does show increased renal iNOS and nitrotyrosine levels and elevated mitochondrial respiration which may be indicative of mitochondrial lipid overfueling. Restricting the high fat diet to decrease adiposity decreased the levels of cellular oxidative stress markers, indicating that adiposity-related proinflammatory changes such as increased iNOS levels may trigger similar responses in the kidney. Mitochondrial respiration remained higher, suggesting that eating excess lipids, despite normal adiposity may still lead to renal mitochondrial overfueling. In comparison, DBA/2J mice developed albuminuria on similar diets, signs of fibrosis, oxidative stress, early signs of podocyte loss (evaluated by the markers podocin and WT-1) and podocyte insulin resistance (unable to phosphorylate their glomerular Akt when insulin was given). To summarize, while the C57BL/6J strain is not particularly susceptible to renal disease, changes in its mitochondrial lipid handling combined with the easy availability of transgenic technology may be an advantage to design new knockout models related to mitochondrial lipid metabolism. The DBA/2J model could serve as a basis for studying podocyte insulin resistance and identifying early renal markers in obesity before more severe kidney disease develops. Based on our observations, we encourage further critical evaluation of mouse models for obesity related chronic kidney disease.

APOL1 G1 genotype modifies the association between HDLC and kidney function in African Americans.

BackgroundDespite evidence of an association between variants at the apolipoprotein L1 gene (APOL1) locus and a spectrum of related kidney diseases, underlying biological mechanisms remain unknown. An earlier preliminary study published by our group showed that an APOL1 variant (rs73885319) modified the association between high-density lipoprotein cholesterol (HDLC) and estimated glomerular filtration rate (eGFR) in African Americans. To further understand this relationship, we evaluated the interaction in two additional large cohorts of African Americans for a total of 3,592 unrelated individuals from the Howard University Family Study (HUFS), the Natural History of APOL1-Associated Nephropathy Study (NHAAN), and the Atherosclerosis Risk in Communities Study (ARIC). The association between HDLC and eGFR was determined using linear mixed models, and the interaction between rs73885319 genotype and HDLC was evaluated using a multiplicative term.ResultsAmong individuals homozygous for the risk genotype, a strong inverse HDLC-eGFR association was observed, with a positive association in others (p for the interaction of the rs73885319 × HDLC =0.0001). The interaction was similar in HUFS and NHAAN, and attenuated in ARIC. Given that ARIC participants were older, we investigated an age effect; age was a significant modifier of the observed interaction. When older individuals were excluded, the interaction in ARIC was similar to that in the other studies.ConclusionsBased on these findings, it is clear that the relationship between HDLC and eGFR is strongly influenced by the APOL1 rs73885319 kidney risk genotype. Moreover, the degree to which this variant modifies the association may depend on the age of the individual. More detailed physiological studies are warranted to understand how rs73885319 may affect the relationship between HDLC and eGFR in individuals with and without disease and across the lifespan.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1645-7) contains supplementary material, which is available to authorized users.

Increased risk of glomerulonephritis and chronic kidney disease in relation to the severity of psoriasis, concomitant medication, and comorbidity: a nationwide population-based cohort study.

Few studies have examined the association between psoriasis and glomerulonephritis (GN) as well as chronic kidney disease (CKD). To determine the risk of CKD in patients with psoriasis and evaluate the impact of the severity of psoriasis, comorbidities and concomitant drugs on the risk of GN and CKD in patients with psoriasis. We identified 4344 patients with psoriasis for the study cohort and randomly selected 13,032 subjects as a control cohort. Each subject was individually followed for up for 5 years to identify those who subsequently developed GN and CKD. After adjustment for traditional CKD risk factors, psoriasis was found to be independently associated with an increased risk of CKD during the follow-up period [hazard ratio (HR) 1.28; 95% confidence interval (CI) 1.14-1.44]. The increased incidence of GN in patients with psoriasis (HR 1.50, 95% CI 1.24-1.81) may contribute to the positive association between psoriasis and CKD. Patients with mild and severe psoriasis had an increased risk of CKD and GN compared with the control cohort; the risk increased with severity. Patients with psoriasis and arthritis exhibited a higher risk of CKD than patients without arthritis (HR 1.62 vs. 1.26). Among drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) have the strongest association with CKD in patients with psoriasis (adjusted odds ratio 1.69, 95% CI 1.14-2.49). Psoriasis was associated with a higher risk of developing CKD and GN. High severity, psoriatic arthritis involvement and concomitant NSAIDs use further increased the risk of CKD in patients with psoriasis.

The relationship between renal volume and histology in obese and nonobese kidney donors.

Obesity and related kidney diseases have become a global epidemic problem. However, the underlying pathogenesis of obesity-related renal diseases has not been clearly understood. In this study, we explored the link between renal volume (RV) determined by computed tomography (CT) and renal histology together with functional parameters in an obese population. Eighty-two kidney donors who underwent CT for the measurement of kidney volume and zero-hour renal biopsy for renal histology were included in this cross-sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h urine specimens as indicators of renal function. Mean body mass index (BMI) was 28 ± 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 ± 36 cm(3). RV was positively correlated with BMI, body surface area and creatinine clearance and negatively with HDL-cholesterol in the whole population. Renal function parameters of obese subjects were better, and their renal volumes were higher compared with the nonobese subjects. In obese subjects, corrected RV was positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r = -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected RV was significantly associated with chronicity index (OR: 0.96; P = 0.01). In obese cases, decreased RV determined by CT is associated with worse renal histology. In this population, kidney imaging techniques may provide important clues about renal survival.

Release and pharmacokinetics of near-infrared labeled albumin from monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) microspheres after subcapsular renal injection

Subcapsular renal injection is a novel administration method for local delivery of therapeutics for the treatment of kidney related diseases. The aim of this study was to investigate the feasibility of polymeric microspheres for sustained release of protein therapeutics in the kidney and study the subsequent redistribution of the released protein. For this purpose, monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres (40μm in diameter) loaded with near-infrared dye-labeled bovine serum albumin (NIR-BSA) were prepared by a membrane emulsification method. Rats were injected with either free NIR-BSA or with NIR-BSA loaded microspheres (NIR-BSA-ms) and the pharmacokinetics of the released NIR-BSA was studied for 3weeks by ex vivo imaging of organs and blood. Quantitative release data were obtained from kidney homogenates and possible metabolism of the protein was investigated by SDS–PAGE analysis of the samples. The ex vivo images showed a rapid decrease of the NIR signal within 24h in kidneys injected with free NIR-BSA, while, importantly, the signal of the labeled protein was still visible at day 21 in kidneys injected with NIR-BSA-ms. SDS–PAGE analysis of the kidney homogenates showed that intact NIR-BSA was released from the microspheres. The locally released NIR-BSA drained to the systemic circulation and subsequently accumulated in the liver, where it was degraded and excreted renally. The in vivo release of NIR-BSA was calculated after extracting the protein from the remaining microspheres in kidney homogenates. The in vivo release rate was faster (89±4% of the loading in 2weeks) compared to the in vitro release of NIR-BSA (38±1% in 2weeks). In conclusion, PLHMGA microspheres injected under the kidney capsule provide a local depot from which a formulated protein is released over a prolonged time-period.

Impact of hyperuricaemia on the chronic kidney disease‐associated risk factors in a community‐based population

Hyperuricaemia is a common finding in subjects with lifestyle related diseases. This study was performed to examine its association with chronic kidney disease (CKD) in relation to other risk factors in a community-based population. Data from 187 914 participants, excepting CKD stage 5, of the health check-up were included in this analysis. The association between CKD and its risk factors were examined by a logistic analysis. The association of hyperuricaemia and CKD was also compared in the population without any lifestyle related diseases and the whole population. The prevalence of hyperuricaemia was significantly higher in the advanced stage of CKD. The odds ratio of hyperuricaemia was higher than that of other factors for the association with CKD. The odds ratio of many CKD-associated variables was increased in the advanced stage. Among them, the odds ratio of hyperuricaemia was markedly increased. The prevalence of hyperuricaemia was lower in the population without any lifestyle related diseases than in the whole population in the early stages, the difference of prevalence between the two populations becoming smaller in the advanced stage. The association of incident CKD with hyperuricaemia was stronger than with other chronic kidney disease-risk factors, this association becoming more significant in the advanced stage of chronic kidney disease. Although this result does not indicate the cause and result relationship, the data suggest that hyperuricaemia might not be appropriately treated in this population.

Immunoglobulin G4-Related Kidney Disease: A Comprehensive Pictorial Review of the Imaging Spectrum, Mimickers, and Clinicopathological Characteristics.

Immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) has recently been demonstrated to be an important part of IgG4-related sclerosing disease (IgG4-SD). However, since IgG4-KD is still relatively unfamiliar to radiologists and physicians as compared to IgG4-SD involving other organs, it could, therefore, be easily missed. In this article, we present a comprehensive pictorial review of IgG4-KD with regards to the imaging spectrum, mimickers, and clinicopathologic characteristics, based on our clinical experience with 48 patients during the past 13 years, as well as a literature review. Awareness of the broad imaging spectrum of IgG4-KD and differential diagnosis from its mimickers will thus facilitate its early diagnosis and treatment.

Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial

Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans. Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2,571 African Americans from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary or carotid artery revascularization) and CKD (eGFR under 60 ml/min/1.73m2 and/or UACR over 30 mg/g). African American SPRINT participants were 45.3% female with mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mmHg, eGFR 76.3 (77.1) ml/min/1.73m2, UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08–1.73) and log UACR estimated slope [β] 0.33) and negatively associated with eGFR (β −3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82–1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not prevalent CVD in African American with a UACR under 1000 mg/g.