Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The "old" cross-talk between kidney and bone (classically known as "renal osteodystrophies") has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of "osteoporosis" emerges in nephrology as a new possibility "if results will impact clinical decisions". Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes.

Diffuse Alopecia and Thyroid Atrophy in Sheep.

Thyroid dysfunction substantially affects the quality of life due to its association with various disorders in different organs. A low intake of selenium and zinc can predispose to thyroid alterations, resulting in hypothyroidism. A deficiency of selenium and zinc causes direct and indirect skin lesions, both by the action of free radicals on the skin and by thyroid dysfunction. The aim of this study was to describe natural cases of diffuse alopecia and thyroid abnormalities in sheep with selenium and zinc deficiency. Five adult sheep presented marked and diffuse alopecia, and the residual hairs were dry and brittle. The skin was thick and crusty, with marked peeling. The triiodothyronine (T3) and thyroxine (T4) serum concentrations were below reference values for the species. Zinc and Se concentrations were low in both the serum and liver. During necropsy, cachexia associated with serous fat atrophy was observed, and the thyroid glands showed marked atrophy. Microscopically, the thyroid presented multifocal to coalescent atrophy, with atrophied and dilated follicles, macrophage infiltration, and the presence of fibrous connective tissue. The skin revealed hyperkeratosis and edema. It is concluded that thyroid atrophy, alopecia, and hyperkeratosis are associated with low serum and liver concentrations of zinc and selenium in sheep.

Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

[High risk pregnancy in patients with extrophy-epispadia complex: Uro-gynecological characteristics and management.] / Embarazo de alto riesgo en pacientes con complejo extrofia-epispadias: características uro-ginecológicas y manejo.

OBJECTIVE: The exstrophy-epispadias complex (EEC) ranges from distal epispadias to cloacal exstrophy, with serious repercussions on the quality of life of patients. However, reconstructive surgery offers the opportunity to reach adulthood and consider motherhood.The objective of this work is to assess the uro-gynecological characteristics and the risks that pregnant women have with EEC. MATERIALS AND METHOD: Retrospective study of 50 patients diagnosed with EEC and treated in a reference center for this pathology, born between 1968 and 2000. Their medical records were reviewed and all demographic, pathological and gynecological data were collected. RESULTS: 37 patients have the inclusion criteria and of these 8 achieved 17 pregnancies (90% spontaneous and 10% through IVF). 10 were successful (50% at term) and 7 were abortions, 87.5% of which were in the first trimester. Urinary tract infection (UTI) was the most frequent complication (41.6%) and the most severe was intestinal occlusion. None of the patients presented renal function impairment during the gestation or dilation of the pathological upper urinary tract (UUT). 62.5% of the patients presented genital prolapses after pregnancies, 80% of which were grade III and IV. 87.5% were dry in the follow-up after their pregnancies. CONCLUSION: Pregnancy in the EEC patients is high risk and it is crucial that the follow-up is carried out by a specialized and integrated multidisciplinary team to minimize complications.

OBJETIVO: El complejo extrofia-epispadias (CEE) abarca desde las epispadias distales hasta la extrofia de cloaca, con serias repercusiones en la calidad de vida de los pacientes; sin embargo, la cirugía reconstructiva ofrece la oportunidad de llegar a la edad adulta y plantearse la maternidad. El objetivo de este trabajo es valorar las características uro-ginecológicas y los riesgos que presentan las gestantes con CEE. MATERIALES Y MÉTODO: Estudio retrospectivo de 50 pacientes diagnosticadas de CEE y tratadas en un centro de referencia para esta patología, nacidas entre 1968 y 2000. Se revisaron sus historias clínicas y se recogieron todos los datos demográficos, patológicos  y ginecológicos. RESULTADOS: 37 pacientes cumplían los criterios de inclusión y de estas 8 lograron 17 embarazos (90% espontáneos y 10% mediante FIV). 10 fueron exitosos (50% a término) y 7 fueron abortos, 87,5% de los cuales fueron en el primer trimestre. La infección urinaria (ITU) fue la complicación más frecuente (41,6%) y la más severa fue la oclusión intestinal. Ninguna de las pacientes presentó deterioro de la función renal durante la gestación o dilatación del tracto urinario superior (TUS) patológica. 62,5% de las pacientes presentaron prolapsos genitales posteriores a los embarazos, 80% de los cuales fueron grado III y IV. 87,5% se encontraban secas en el seguimiento posterior a sus embarazos. CONCLUSIÓN: El embarazo en el CEE es de alto riesgo y es crucial que el seguimiento sea llevado a cabo por un equipo multidisciplinar especializado e integrado para minimizar las complicaciones.