Progression of glomerular diseases: Is the podocyte the culprit? The stereotyped development of the glomerular lesions in many animal models and human forms of progressive renal disease suggests that ...there are common mechanisms of disease progression. We propose the outline of such a mechanism based on following aspects: (1) The glomerulus is a complex structure, the stability of which depends on the cooperative function of the basement membrane, mesangial cells and podocytes, counteracting the distending forces originating from the high glomerular hydrostatic pressures. Failure of this system leads to quite uniform architectural lesions. (2) There is strong evidence that the podocyte is incapable of regenerative replication post-natally; when podocytes are lost for any reason they cannot be replaced by new cells. Loss of podocytes may therefore lead to areas of “bare” GBM, which represent potential starting points for irreversible glomerular injury. (3) Attachment of parietal epithelial cells to bare GBM invariably occurs when bare GBM coexists with architechtural lesions, leading to the formation of a tuft adhesion to Bowman's capsule, the first “committed” lesion progressing to segmental sclerosis. (4) Within an adhesion the tuft merges with the interstitium, allowing filtration from perfused capillaries inside the adhesion towards the interstitium. The relevance of such filtration is as yet unclear but may play a considerable role in progression to global sclerosis and interstitial fibrosis.
Purpose
The perception of pain in response to a noxious stimulus can be markedly reduced following an acute bout of exercise exercise-induced hypoalgesia (EIH). Sex differences in EIH frequently ...occur after exercise but may be confounded by the sex differences in muscle fatigue. The purpose was to determine if sex differences in pain relief occur after an exercise protocol when muscle fatigue is similar for both young and older men and women.
Methods
Pain perception of 33 men (15 young) and 31 women (19 young) was measured using a pressure pain stimulus on the left index finger before and after maximal velocity concentric contractions of knee extensors or elbow flexors (separate days). During the 2-min pressure pain test, participants verbally indicated the onset of pain (pain threshold) and reported pain intensity (0–10) every 20 s.
Results
Only women experienced an increase in pain threshold (30 ± 27 to 41 ± 32 s) following elbow flexor exercise (trial × sex:
p
= 0.03). Neither men nor women experienced an increase in pain threshold following knee extensor exercise, and pain ratings were unchanged after exercise with either limb (
p
> 0.05). The pain response to exercise was similar in young and older adults (trial × age:
p
> 0.05), despite older adults demonstrating greater fatigability than young adults for the elbow flexor and knee extensor exercise tasks.
Conclusions
Under controlled conditions where muscle fatigue is similar, sex differences in EIH occur in young and older adults that is site specific (upper extremity). Only women experience EIH following acute single limb high-velocity contractions.
Background
In single-center studies, both preterm birth and low birth weight (LBW) are associated with worse outcomes in childhood nephrotic syndrome. Using the Nephrotic Syndrome Study Network ...(NEPTUNE) observational cohort, we tested the hypothesis that in patients with nephrotic syndrome, hypertension, proteinuria status, and disease progression would be more prevalent and more severe in subjects with LBW and prematurity singly or in combination (LBW/prematurity).
Methods
Three hundred fifty-nine adults and children with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) and available birth history were included. Estimated glomerular filtration rate (eGFR) decline and remission status were primary outcomes, and secondary outcomes were kidney histopathology, kidney gene expression, and urinary biomarkers. Logistic regression was used to identify associations with LBW/prematurity and these outcomes.
Results
We did not find an association between LBW/prematurity and remission of proteinuria. However, LBW/prematurity was associated with greater decline in eGFR. This decline in eGFR was partially explained by the association of LBW/prematurity with
APOL1
high-risk alleles, but the association remained after adjustment. There were no differences in kidney histopathology or gene expression in the LBW/prematurity group compared to normal birth weight/term birth.
Conclusion
LBW and premature babies who develop nephrotic syndrome have a more rapid decline in kidney function. We did not identify clinical or laboratory features that distinguished the groups. Additional studies in larger groups are needed to fully ascertain the effects of (LBW) and prematurity alone or in combination on kidney function in the setting of nephrotic syndrome.
Background
In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that ...hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response.
Methods
A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia.
Results
Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time.
Conclusions
Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Fibromyalgia (FM), a rheumatological disorder of unknown origin, is characterized by both physical and psychological symptoms. Although inconclusive results have been reported for most treatment ...modalities, exercise appears to have universal support for decreasing the myriad of symptoms associated with FM. Weaknesses in the literature, however, prevent conclusive statements regarding exercise prescription and concomitant impact on FM symptomology.
The current pilot study attempted to examine the effect of a 24-wk walking program at predetermined intensities on FM.
Initial design was a randomized control trial with high- and low-intensity exercise groups, and a control group. Subsequent nonrandomized control trials were based on actual exercise behavior.
No differences between initial groups were identified. By collapsing groups, heart rate (HR) decreased (P < 0.05) weeks 0-12. Functional impairments were reduced 54% weeks 0-24, with exercise having a large impact (omega2 = 0.30) on this decrease. By reassigning groups, impact of FM on current health status decreased in the low-intensity group (P < 0.05) and increased in the high-intensity group (P < 0.02) weeks 0-24. Omega squared indicated strong influence of exercise on pain (omega2 = 0.51), with greater pain in the high-intensity group.
A larger number of subjects and direct supervision of the training program to increase compliance is necessary to clarify the effects of a walking program on the manifestations of FM. Results indicate that intensity of the walking program is an important consideration. Individuals with FM can adhere to low-intensity walking programs two to three times per week, possibly reducing FM impact on daily activities.
Abstract Specific pediatric allocation schemes can not only lead to minimization of waiting time, but also to better clinical outcomes for children with end-stage renal disease. The outcome of 4125 ...deceased donor kidney transplants (DDKT) aged 5–35 years were compared with those of 6456 living donor kidney transplants (LDKT) using univariate and multivariate Cox regression analyses. Unadjusted graft survival rates of DDKT were significantly lower than those of LDKT (hazards ratio HR = 1.53; P < .001). Chronic rejection was reported in 416 (10.1%) of 4125 in the DDKT group compared with 537 (8.3%) of 6456 in the LDKT group ( P < .001). Among African American recipients, 67 (3.4%) grafts were lost due to noncompliance as a contributory cause of failure compared with 126 (1.5%) among other races ( P < .001). A significantly lower incidence of noncompliance was observed in children (0.9%) compared with adolescents (2.2% in ages 10–14; P < .001) and high teens (2.0% in ages 15–20; P < .001). Multivariate analysis showed that adjusted graft survival rates of LDKT were superior to DDKT (HR = 1.22; P < .001) after adjusting for recipient race, recipient age, regraft status, and HLA mismatch. The differences of long-term graft survival rates between DDKT and LDKT have not been reduced (4% at 1 year, 10% at 3 years, and 12% at 5 years for unadjusted survival rates and 3% at 1 year, 6% at 3 years, and 9% at 5 years adjusted survival rates). In our analysis presented here the difference in graft survival between LDKT and DDKT has doubled compared with earlier analysis. Therefore, we recommend LDKT whenever possible as a first choice for pediatric transplant recipients.
The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this ...conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject.
The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described.
These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome.
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