Renal Filtration Research Articles

Iron Is Filtered by the Kidney and Is Reabsorbed by the Proximal Tubule.

The aim of this study was to determine the iron (Fe) concentration profile within the lumen of the S2 renal proximal convoluted tubule (PCT) and to resolve whether this nephron segment transported Fe. To do this, we performed in vivo renal micropuncture on Wistar rats, collected PCT tubular fluid from superficial nephrons, and measured Fe concentration. The Fe concentration profile along the S2 PCT suggested significant Fe reabsorption. Proximal tubules were also microperfused in vivo with physiological solutions containing Fe and Zn, Cu, Mn, or Cd. PCTs perfused with 12μmol.l−1 55FeCl3 reabsorbed 105.2±12.7 fmol.mm−1.min−1 Fe, 435±52pmol.mm-1.min−1 Na, and 2.7±0.2nl.mm−1.min−1 water (mean ± SEM; n=19). Addition of ascorbate (1mmol.l−1) to the perfusate did not significantly alter Fe, Na, or water reabsorption. Supplementing the control perfusate with 60μmol.l−1 FeSO4 significantly decreased 55Fe uptake. Recalculating for the altered molar activity following addition of unlabeled Fe revealed a three-fold increase in Fe flux. Addition to the perfusate 12μmol.l−1 CuSO4, MnSO4, CdSO4, or ZnSO4 did not affect Fe, Na, or water flux. In conclusion, (1) in vivo, S2 PCTs of rat reabsorb Fe and (2) Fe is reabsorbed along the PCT via a pathway that is insensitive to Cu, Mn, Cd, or Zn. Together, these data demonstrate for the first time the hitherto speculated process of renal Fe filtration and subsequent tubular Fe reabsorption in a living mammal.

Body Mass Index and Kidney Donor Profile Index as Prognostic Markers of the Outcome of Renal Transplantation

The aim of this study was to determine the effects of Kidney Donor Profile Index (KDPI) and body mass index (BMI) of the deceased donor on the kidney allograft outcome 1 year after transplantation. We retrospectively studied 98 deceased kidney allograft donors with a mean age of 56 ± 12 years. The donors were divided into 5 groups according to their BMI: Normal ΒΜΙ=25 (n=25); ΒΜΙ 25 to 29=Overweight (n=33); ΒΜΙ 30 to 34.9=Obese class I (n=19); ΒΜΙ 35 to 39=Obese class ΙΙ (n=11); and ΒΜΙ >40=Obese class III (n=10). We examined the impact of the deceased donor's BMI and KDPI on delayed graft function (DGF) and estimated renal glomerular filtration rate (eGFR) (measured by the Chronic Kidney Disease Epidemiology Collaboration equation) 1 year after transplantation. Donor BMI significantly increased the prevalence of DGF (P=.031), and it was associated with higher cold ischemia time (P=.021). However, there was no significant association between the aforementioned BMI groups and 1-year eGFR (P=0.57), as deceased grafts from donors with increased BMI (BMI > 40) gained sufficient renal function during the first year of transplantation. Moreover, high KDPI was associated not only with DGF (P=.015), but also with decreased values of eGFR (P=.033). In this population, we identified no significant association between donor BMI and long-term clinical outcomes in deceased donor kidney transplants. KDPI, and not ΒΜΙ, of the deceased donor seems to be a good prognostic factor of renal function at the end of the first year after kidney transplant, whereas high BMI and high KDPI markedly induce DGF.

Commentary on Intraglumerular dysfunction predicts kidney failure in the type 2 diabetes.

The key physiological parameters that determine glomerular filtration rate levels are renal plasma flow, filtration fraction, intraglomerular pressure, and balance between afferent and efferent glomerular arteriolar resistance. The evaluation of the balance between afferent and efferent glomerular arteriolar resistance might be useful for the classification of diabetic kidney disease.

Diagnostic Role of Dopplerography of Renal Vessels in Patients with Late Dysfunction of the Transplanted Kidney

Aims: Search for non-invasive methods for diagnosing late transplant kidney dysfunction, which can improve control and monitor the condition of the kidney transplant, characterization diagnostic role of dopplerography of renal vessels in patients with late dysfunction of the transplanted kidney.
 Study design: When conducting dopplerometry, blood flow indices were analyzed from 3 to 6 cycles of heart contractions, followed by an averaged indicator. In addition, the linear blood flow velocity was assessed separately from the renal vein.
 Place and Duration of Study: For the period 2016-2017 Ultrasound of an allopod was performed in 60 recipients of RT (RENAL TRANSPLANT) in the late postoperative period.
 Methodology: The average age of the patients was 38.89 ± 1.52 years. There were 34 men (56.6 7%), 26 women (43.33%). All patients were divided into two groups: patients with preserved function and patients with RT (RENAL TRANSPLANT) dysfunction. Related kidney transplantation (RRT) was performed in 55.0% of patients, in 45.0% - cadaveric kidney transplantation (CKP). The groups were comparable in the main clinical and demographic parameters.
 Results: The reverse dynamics was observed when examining the level of the renal filtration function indicator, the estimated glomerular filtration rate (SKF) - at a TAMX level of more than 15 cm/sec, glomerular filtration was 51.18 ± 1.93 (47.32-55.04) ml/min (p <0.01), and with a decrease in TAMX of less than 15 cm/sec, the level of SKF decreased significantly, more than twice, to the level of 25.40 ± 2.19 (21.02-29.78) ml/min <0.001).
 Conclusion: The determination of dopplerographic parameters for TP with preserved and especially with impaired depuration function with a direct assessment of TAMX opens up wide opportunities in non-invasive assessment of RT (RENAL TRANSPLANT) changes, identification of developing complications, as well as improved transplant survival.

Human Serum Albumin: A Novel Drug Delivery Carrier System

Serum albumin, often referred to simply as albumin, is a globular protein that in humans is encoded by the ALB gene. Albumin is a multifaceted, highly soluble, stable, nontoxic, non-poisonous, biocompatible and biodegradable plasma protein. Albumin has been widely studied as a protein carrier for drug delivery. Because of its versatile nature, it can also be used for the delivery of the hormones, metals and fatty acids by binding to its specific binding sites. Various studies revealed that albumin can be used to increase the circulating half-life and bioavailability of drug molecules which are smaller than the renal filtration threshold and are rapidly lost from the circulation leading to limiting therapeutic potential. This review article presents advantages, disadvantages, functions, importance, different nanoparticles that can be crowned with an albumin and the special features of albumin as a drug carrier, and how the understanding of these features is currently being employed to optimize the circulatory half-life albumin.

Probing the Relationship Between Declining Renal Glomerular Filtration Over the Life Span and General Biological Aging: Does the Former Provide Means to Estimate the Latter?

Background: While a consistent, gradual decline in the renal glomerular filtration rate (GFR) is a characteristic occurrence over the human life span, the exact pathophysiology behind this event remains unresolved. Evidence to date suggests that the endogenous glucose-insulin system could be involved at some level. Diabetic-induced nephropathy, one of the most prevalent chronic renal diseases, is closely linked to a severe form of insulin resistance (IR). Nevertheless, it is less certain that the ubiquitous milder forms of IR in nondiabetics ascribed customarily to routine, poor choices in diet and exercise management can over time diminish GFR and adversely influence other renal functions to any perceptible extent. Methodology: Baseline data for cross-sectional analyses were obtained from a cohort of healthy, nondiabetic volunteers (fasting blood glucose [FBG] ≤ 125 mg/dL) involved in prior clinical studies. Slope-based rather than threshold analyses were mainly employed. These measurements were applied for the most part to correlate age, FBG levels used as an estimate of IR activity, and systolic blood pressure (SBP) to a variety of metabolic parameters during aging with a primary focus on GFR. Results: Considering cause and effect, FBG and SBP correlate positively with the diminishing GFR over a major part of the life span. The decline in GFR begins somewhere around the mid-20s and coincides with key temporal increases in FBG and SBP levels. Conclusions: A close time-based setting suggests that IR plays a prominent role in the declining GFR that occurs over the life span. This is perhaps due in part through deleterious effects of rising levels of insulin, glucose, and SBP individually or combined that are also popular proposed causative factors for human aging in general. On the philosophical side, the latter fact suggests that the declining GFR might provide a practical way to estimate the rate of overall human biological aging.

Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine

BackgroundType 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail.MethodsPatients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model.ResultsTreatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both padjust < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (RA) (p = 0.116), but diminished resistance of efferent arterioles (RE) (p = 0.001). In M+I group RA was increased (p = 0.006) and RE remained unchanged (p = 0.538). The effects on RA (padjust < 0.05) and on RE (padjust < 0.05) differed between the groups.ConclusionsIn patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing RA and E+L predominantly decreasing RE, which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects.Trial registration: The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016

Hyperglycemia alters mitochondrial respiration efficiency and mitophagy in human podocytes

Podocytes constitute the outer layer of the renal glomerular filtration barrier. Their energy requirements strongly depend on efficient oxidative respiration, which is tightly connected with mitochondrial dynamics. We hypothesized that hyperglycemia modulates energy metabolism in glomeruli and podocytes and contributes to the development of diabetic kidney disease. We found that oxygen consumption rates were severely reduced in glomeruli from diabetic rats and in human podocytes that were cultured in high glucose concentration (30 mM; HG). In these models, all of the mitochondrial respiratory parameters, including basal and maximal respiration, ATP production, and spare respiratory capacity, were significantly decreased. Podocytes that were treated with HG showed a fragmented mitochondrial network, together with a decrease in expression of the mitochondrial fusion markers MFN1, MFN2, and OPA1, and an increase in the activity of the fission marker DRP1. We showed that markers of mitochondrial biogenesis, such as PGC-1α and TFAM, decreased in HG-treated podocytes. Moreover, PINK1/parkin-dependent mitophagy was inhibited in these cells. These results provide evidence that hyperglycemia impairs mitochondrial dynamics and turnover, which may underlie the remarkable deterioration of mitochondrial respiration parameters in glomeruli and podocytes.

How Low Can You Go? Safety and Efficacy of Sodium-Glucose Cotransporter Inhibitors in Decreased Renal Function

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of medications primarily used as either monotherapy or add-on therapy in those with type 2 diabetes. Given the mechanism of SGLT2 inhibitors, a renal dose adjustment or glomerular filtration rate cutoff in which it should be avoided due to decreased efficacy is recommended. However, studies have shown that these agents may possess renal benefits through decreasing serum glucose levels as well as decreasing intraglomerular pressure and albuminuria. The safety and benefits of SGLT2 inhibitors in patients with decreased renal function is an area of uncertainty.

Diclofenac toxicity in susceptible bird species results from a combination of reduced glomerular filtration and plasma flow with subsequent renal tubular necrosis.

Diclofenac caused the death of millions of vultures on the Asian subcontinent. Other non-steroidal anti-inflammatory drugs (NSAIDs) have since also been shown to be toxic to vultures with the exception of meloxicam. For this study, we evaluated the effect of diclofenac on renal uric acid transport and glomerulus filtration in an acute toxicity model. In a two-phase study with the same birds, healthy chickens (a validated model species) were treated intravenously with para-amino hippuric acid (PAH) and iohexol (IOH) in combination in phase 1. In phase 2, the same PAH and IOH combination was then combined with diclofenac (10 mg/kg). In both phases, blood and faeces were sequentially collected. In phase 1, the birds showed no signs of ill health. Moreover, PAH, IOH and uric acid clearance was rapid. In phase 2, two chickens showed early signs of hyperuricemia 8 hours after exposure and died approximately 24h later. Necropsy showed classic signs of renal damage and gout. Diclofenac had a rapid plasma half-life of elimination of less than 2 hours indicating that toxicity was likely due to an irreversible destruction of a physiological process. All the birds in phase 2 had decreased uric acid, PAH and IOH clearance in comparison to phase 1. The decrease in PAH clearance was variable between the birds (average of 71%) but was near 98% reduced in the two birds that died. It is concluded that diclofenac alters both renal perfusion and renal plasma flow, with death associated with tubular secretion being reduced to negligible functionality for a prolonged period. This would support previous in vitro findings of early cell death from ROS accumulation. However, further evaluation is needed to elucidate this final step.

The Shrunken pore syndrome is associated with poor prognosis and lower quality of life in heart failure patients: the HARVEST‐Malmö study

AimsThis study aimed to investigate the association between the ‘Shrunken pore syndrome’ (SPS) and risk of death, 30 day rehospitalization, and health‐related quality of life (QoL) in heart failure (HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatin C/eGFRcreatinine ratio.Methods and resultsA total of 373 patients hospitalized for HF [mean age 74.8 (±12.1) years; 118 (31.6%) women] were retrieved from the HeARt and brain failure inVESTigation trial (HARVEST‐Malmö). Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formulas were used for estimation of glomerular filtration rate (eGFR). Presence of SPS was defined as eGFRcystatin C ≤ 60% of eGFRcreatinine. In Cox regression multivariate models, associations between SPS, risk of death (median follow‐up time 1.8 years), and risk of 30 day rehospitalization were studied. Associations between SPS and impaired QoL were studied using multivariate logistic regressions. In multivariate models, SPS was associated with all‐cause mortality [124 events; hazard ratio (HR) 1.99; 95% confidence interval (95% CI) 1.23–3.21; P = 0.005] and with 30 day rehospitalization (70 events; HR 1.82; CI 95% 1.04–3.18; P = 0.036). Analyses of QoL, based on a Kansas City Cardiomyopathy Questionnaire overall score < 50, revealed that SPS was associated with higher risk of low health‐related QoL (odds ratios 2.15; CI 95% 1.03–4.49; P = 0.042).ConclusionsThe results of this observational study show for the first time an association between SPS and poor prognosis in HF. Further studies are needed to confirm the results in HF cohorts and experimental settings to identify pathophysiological mechanisms.

Nanotechnology, Nanomedicine, and the Kidney

The kidneys are vital organs performing several essential functions. Their primary function is the filtration of blood and the removal of metabolic waste products as well as fluid homeostasis. Renal filtration is the main pathway for drug removal, highlighting the importance of this organ to the growing field of nanomedicine. The kidneys (i) have a key role in the transport and clearance of nanoparticles (NPs), (ii) are exposed to potential NPs’ toxicity, and (iii) are the targets of diseases that nanomedicine can study, detect, and treat. In this review, we aim to summarize the latest research on kidney-nanoparticle interaction. We first give a brief overview of the kidney’s anatomy and renal filtration, describe how nanoparticle characteristics influence their renal clearance, and the approaches taken to image and treat the kidney, including drug delivery and tissue engineering. Finally, we discuss the future and some of the challenges faced by nanomedicine.

TME-Responsive Multistage Nanoplatform for siRNA Delivery and Effective Cancer Therapy.

Since the discovery of RNA interference (RNAi), RNAi technology has rapidly developed into an efficient tool for post-transcriptional gene silencing, which has been widely used for clinical or preclinical treatment of various diseases including cancer. Small interfering RNA (siRNA) is the effector molecule of RNAi technology. However, as polyanionic macromolecules, naked siRNAs have a short circulatory half-life (<15 min) and is rapidly cleared by renal filtration, which greatly hinders their clinical application. Furthermore, the anionic and macromolecular characteristics of naked siRNAs impede their readiness to cross the cell membrane and therefore delivery vehicles are required to facilitate the cellular uptake and cytosolic delivery of naked siRNAs. In the past decade, numerous nanoparticles (NPs) such as liposomes have been employed for in vivo siRNA delivery, which have achieved favorable therapeutic outcomes in clinical disease treatment. In particular, because tumor microenvironment (TME) or tumor cells show several distinguishing biological/endogenous factors (eg, pH, enzymes, redox, and hypoxia) compared to normal tissues or cells, much attention has recently paid to design and construct TME-responsive NPs for multistaged siRNA delivery, which can respond to biological stimuli to achieve efficient in vivo gene silencing and better anticancer effect. In this review, we summarize recent advances in TME-responsive siRNA delivery systems, especially multistage delivery NPs, and discuss their design principles, functions, effects, and prospects.

Angiotensin II-induced natriuresis is attenuated in knockout mice lacking the receptors for tumor necrosis factor-α.

Intravenous infusion of relatively higher doses of angiotensin II (AngII) elicits natriuresis as opposed to its usual anti‐natruretic response. As AngII can induce tumor necrosis factor‐α (TNFα) production which elicits natriuresis via its action on TNFα receptor type 1 (TNFR1), we hypothesize that the concomitant release of TNFα contributes to the natriuretic response to AngII. Responses to AngII infusion (1 ng min−1 g−1 for 75 min, iv) were evaluated in anesthetized knockout (KO) mice lacking TNFR1 (n = 6) and TNFR2 (TNFα receptor type 2; n = 6) and compared these responses with those in wild type (WT; n = 6) mice. Arterial pressure (AP) was recorded from a cannula placed in the carotid artery. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by PAH and inulin clearances, respectively. Urine was collected from a catheter placed in the bladder. AngII caused similar increases (p < 0.05 vs basal values) in AP (WT, 37 ± 5%; TNFR1KO, 35 ± 4%; TNFR2KO, 30 ± 4%) and decreases (p < 0.05) in RBF (WT, −39 ± 5%; TNFR1KO, −28 ± 6%; TNFR2KO, −31 ± 4%) without significant changes in GFR (WT, −17 ± 7%; TNFR1KO, −18 ± 7%; TNFR2KO, −12 ± 7%). However, despite similar changes in AP and renal hemodynamics, AngII induced increases (p < 0.05) in urinary sodium excretion in WT (3916 ± 942%) were less in the KO strains, more or less in TNFR1KO (473 ± 170%) than in TNFR2KO (1176 ± 168%). These data indicate that TNF‐α receptors, particularly TNFR1 are involved in the natriuretic response that occur during acute infusion of AngII and thus, plays a protective role in preventing excessive salt retention at clinical conditions associated with elevated AngII level.

In The Absence Of Cardiometabolic Diseases Is Age An Independent Factor In Assessing Renal Health And Function? A Pilot Study

Estimated glomerular filtration rate (eGFR) is a measure of renal filtration and clearance of serum creatinine and is conventionally used to characterize the progressive decline in renal function (RF). Assessment of RF and renal health (RH) is traditionally believed to be age-dependent. However, in the absence of cardiometabolic diseases (hypertension, diabetes, hyperlipemia, etc.), this may not be the case. Recently, novel markers of RH and RF support the notion that age is a secondary factor influencing renal decline. PURPOSE: To determine the magnitude of age as an influencing factor involved in the decline of RF with novel markers of RH and function in the absence of cardiometabolic risk factors. METHODS: Fifty-four participants (n = 27 men; n = 27 women; age 33.4 + 12.5 yr; height 171.7 + 10.9 cm; weight 77.9 + 15.9 kg; BMI 26.5 + 5.5; SBP 120 + 10.4; DBP 77.7 + 6.7; CHOL 174 + 30; and GLU 95 + 7) completed a single health assessment to quantify renal health and function. Blood and urine samples were collected by the same technician under standardized conditions and stored at -80 °C until project completion. Serum creatinine (sCR), urine creatinine (uCr), cystatin C (CyC), and urine epidermal growth factor (uEGF) were used to calculate estimates of renal health and function via uEGF/uCr ratio (uEGFR), eGFR - modification of diet in renal disease (MDRD), CKD-EPI, and SCr/CyC eGFR. Renal health and function markers were analyzed and compared in age groups (20s, 30s, 40s, 50s) using 4 (group) by 1 (sample) ANOVAs. RESULTS: There were no significant differences between age groups in the biomarkers and estimates of RH and RF. sCR (F = 0.17, p = 0.91), uEGF (F = 0.87, p = 0.46), CyC (F = 1.98, p = 0.13), CyC eGFR (F = 2.81, p = 0.10), MDRD (F = 2.08, p = 0.12), CKD-EPI (F = 0.34, p = 0.80), and SCr/CyC eGFR (F = 2.05, p = 0.12). uEGFR was significantly different between (F = 1.93, p = 0.14) different between age groups. uCr was significantly different ((F = 5.33, p = 0.003) between 40s and 50s. CONCLUSION: Changes in RH and RF appear to be independent of age in the absence of cardiometabolic diseases, indicates RH and RF could potentially be maintained in adulthood, middle age, and possibly attenuated in the senior years with the continued absence of cardiometabolic diseases.

Ameliorative, Antioxidant and Immunomodulatory Potential of Vitamin D on Aminoglycoside Induced Acute Kidney Injury in Wistar Rats

Background: Acute kidney injury causes an abrupt decline in renal filtration and affects animals in a similar way to humans. Diagnosis can be made based on urinalysis, serum biochemistry and various biomarkers. The present study was conducted to evaluate the ameliorative, antioxidant and immunomodulatory potential of vitamin D in rats induced with acute kidney injury. Methods: In the present study, group A rats were taken as healthy control, group B rats were given gentamicin @ 100 mg/kg BW intraperitoneally for 8 days and were considered as disease control and group C rats were treated with Vitamin D @ 0.4 µg/kg/day subcutaneously for 8 days along with intraperitoneal gentamicin injection. Reduced glutathione (GSH), lipid peroxide (LPO), catalase and superoxide dismutase (SOD) were estimated in erythrocytes on day 0, 4 and 8. Tumor necrosis factor alpha (TNF α) and interleukin 10 (IL 10) were also estimated along with urine and serum biochemistry on day 0, 4 and 8. Kidney tissue samples were collected on day 8 for histopathological examination. Result: The mean values of GSH, catalase and SOD were significantly (P less than 0.05) higher whereas the mean value of LPO was significantly (P less than 0.05) lower in group C compared to group B on day 4 and 8. On day 4 and 8, the mean value of TNF α was significantly (P less than 0.05) lower, while the mean value of IL-10 was significantly (P less than 0.05) higher in rats treated with vitamin D as compared to disease control. Histopathological examination along with urine and serum biochemistry revealed protective efficacy of vitamin D in acute kidney injury. Based on the findings of the present study, it is concluded that vitamin D is having ameliorative efficacy along with antioxidant and immunomodulatory potential in case of gentamicin induced acute kidney injury in Wistar rats. However, detailed studies are required to explore the therapeutic potential of vitamin D in clinical cases of kidney diseases.

Imaging Reveals Importance of Shape and Flexibility for Glomerular Filtration of Biologics.

Advances in antibody engineering have enabled the construction of novel molecular formats in diverse shapes and sizes, providing new opportunities for cancer immunotherapeutic drug discovery while also revealing limitations in knowledge of structure-activity relationships. The current understanding of renal filtration originates largely from data reported for dextrans, IgG, albumin, and selected globular proteins. For a one-armed IgG-based T-cell imaging agent, we observed higher renal signal than typically observed for bivalent IgGs, prompting us to explore the factors governing renal filtration of biologics. We constructed a small representative library of IgG-like formats with varied shapes and hinge flexibilities falling broadly into two categories: branched molecules including bivalent IgG and (scFv)2Fc, and nonbranched molecules including one-armed IgG, one-armed IgG with stacked Fab, and one-armed IgG with a rigid IgA2 hinge. Transmission electron microscopy revealed Y-shaped structures for the branched molecules and pseudo-linear structures for the nonbranched molecules. Single-photon emission CT imaging, autoradiography, and tissue harvest studies demonstrated higher renal uptake and catabolism for nonbranched molecules relative to branched molecules. Among the nonbranched molecules, the one-armed IgG with rigid IgA2 hinge molecule demonstrated higher kidney uptake and decreased systemic exposure relative to molecules with a more flexible hinge. Our results show that differences in shape and hinge flexibility drive the increased glomerular filtration of one-armed relative to bivalent antibodies and highlight the practical advantages of using imaging to assess renal filtration properties. These findings are particularly relevant for T-cell-dependent bispecific molecules, many of which have nonstandard antibody structures.

In the absence of cardiometabolic diseases, is age an independent factor in assessing renal health and filtration? A pilot study

Introduction: Serum creatinine (sCr) is conventionally used to characterize the progressive decline in renal filtration (RF). Assessment of RF and renal health (RH) is traditionally believed to be agedependent. However, in the absence of cardiometabolic disease (CMD), this may not be the case. Objectives: The purpose of this study was to determine the magnitude of age as an influencing factor independent of CMD with novel markers of RH/RF in a single health assessment. Patients and Methods: Fifty-four participants (n = 27 men; n = 27 women; age 33.4 ± 12.5 years; BMI 26.5 ± 5.5; SBP 120 ± 10.4; DBP 77.7 ± 6.7; CHOL 174 ± 30) free of CMD were recruited to assess sCr, urine creatinine (uCr), cystatin C (CyC), and urine epidermal growth factor (uEGF) to calculate estimates of RH/F via uEGF/uCr ratio (uEGFR), eGFR - modification of diet in renal disease (MDRD), CKD-EPI, and sCr/CyC eGFR. Results: There were no significant differences between age groups (20s, 30s, 40s, 50s) in biomarkers and estimates of RH/RF, sCr (P=0.91), uEGF (P=0.46), CyC (P=0.13), CyC eGFR (P= 0.10), MDRD (P=0.12), CKD-EPI (P=0.80), and sCr/CyC eGFR (P=0.12). Post-hoc analysis revealed uEGFR was the only significantly different variable between 40s and 50s age groups (P= 0.02). Conclusion: Changes in RH/RF appear to be independent of age in the absence of CMD. Indicating RH/RF could potentially be maintained in adulthood and throughout the older adult years with the continued absence of CMD.

The efficacy evaluation of partial nephrectomy with selective renal artery branch occlusion by laparoscopy.

Background:To investigate the clinical application and effect of laparoscopic partial nephrectomy with renal artery branch occlusion in the treatment of early renal tumors.Methods:A retrospective analysis was conducted on the clinical data of 15 cases of renal tumor patients who underwent partial nephrectomy by laparoscopic selective renal artery branch occlusion in our department from January 2017 to January 2018. Nine male patients and 6 female patients were aged 46 to 65 years, with an average age of 54.3 ± 7.2 years. The diameters of tumors were 2.2 to 4.0 cm, with an average of 3.3 ± 0.7 cm. There are 10 tumors locating on the left side and 5 on the right side. Preoperative renal glomerular filtration rate (GFR) were 77.3 to 61.9 mL/min with an average of 47.6 ± 7.5 mL/min. All patients’ diseased kidneys underwent renal computer tomography angiography examination before surgery. And the diseased kidney underwent reexamination of renal GFR. The operation time, renal artery branch occlusion time, intraoperative blood loss, postoperative hospital stay, changes of renal function, and complications were evaluated.Results:All surgery were completed successfully, the surgery time was 136.7 ± 15.2 min, intraoperative renal artery branch occlusion time was 21.3 ± 4.5 min, the intraoperative blood loss was 223.3 ± 69.5 mL, the postoperative hospital stay was 6.5 ± 1.7 days, and the postoperative 1-month GFR was 49.5 ± 6.6 mL/min. There was no significant difference between the renal GFR before and after surgery (P > .05). There was no blood transfusion and transfer open surgery cases. The patients were followed up for 3 to 15 months without complications.Conclusions:Partial nephrectomy with selective renal artery branch occlusion by laparoscopy is a safe, feasible, and effective method for the treatment of early renal cancer. It makes good use of the technical advantages of clear operation field and fine operation of laparoscopic surgery, avoids the heat ischemia process of the whole kidney, and can better protect the renal function.

Low-Intensity Shockwave Therapy (LI-ESWT) in Diabetic Kidney Disease: Results from an Open-Label Interventional Clinical Trial.

PurposeTreatment with low-intensity shockwave therapy (LI-ESWT) is associated with angiogenesis and is suggested as a treatment for different types of vascular diseases. It was hypothesized that LI-ESWT improves the renal filtration barrier and halts the progression of GFR decline in diabetic kidney disease (DKD) potentially through VEGF and NO formation. We present the first data on LI-ESWT in human DKD.MethodsThe study was designed as an interventional, prospective, one-arm, Phase 1 study. We investigated change in GFR and albuminuria in 28 patients with DKD treated with six sessions of LI-ESWT over three weeks. The patients were followed for six months. Urine excretion of kidney injury markers, vascular endothelial growth factor (VEGF) and nitric oxide metabolites (NOx) was studied after LI-ESWT.ResultsThere were no significant changes in GFR and albuminuria up to six months after LI-ESWT compared to baseline. Urine VEGF was transiently reduced one month after LI-ESWT, but there were no other significant changes in urine VEGF or NOx after LI-ESWT. Secondary analysis showed that NOx increased after LI-ESWT in patients who had low levels of NOx at baseline. Kidney injury marker trefoil factor 3 (TFF3) increased acutely after the first session of LI-ESWT indicating transient endothelial repair. Other markers of kidney injury were stable in relation to LI-ESWT.ConclusionLI-ESWT treatment did not significantly improve kidney function and albumin excretion. It is concluded that LI-ESWT is not harmful. A randomized blinded study should be performed to clarify whether adjunctive treatment with LI-ESWT is superior to standard treatment of DKD.