Antiphospholipase A2 receptor antibody-positive membranous nephropathy in the kidney donor: Lessons from a serendipitous transplantation.

Primary membranous nephropathy (PMN) is an autoimmune disease limited to the kidney that is characterized by the presence of circulating PLAR2 antibodies in 70% of the cases and usually positivity for PLA2R and IgG4 by immunohistochemistry (IHC) staining. We report the first documented case of PMN (PLA2R positive) in a deceased kidney donor, transplanted to two different recipients and their clinical and immunological evolution through serial biopsies. Recipient A's first allograft biopsy (Day 26) was compatible with a MN with both positive PLA2R and IgG4 subepithelial deposits in IHC. The donor's preimplantation kidney biopsies were retrieved and reexamined, revealing MN, with high intensity for PLA2R and IgG4 in IHC. Recipient B's protocol allograft biopsy, performed later at 3 months, also revealed histology compatible with MN but without the presence of PLA2R nor IgG4 in IHC. At 1-year follow-up, both recipients maintain graft function. Serial protocol biopsies were performed in both patients showing disappearance of IgG4 in recipient A but the persistence of PLA2R in IHC. We can conclude that, given the reversal of PMN changes in the grafts, it could be considered to transplant a patient from an asymptomatic deceased donor with PMN as long as he maintains unaltered renal function.

Bone Mineral Disease After Kidney Transplantation.

Chronic kidney disease-mineral bone disorder (CKD-MBD) after kidney transplantation is a mix of pre-existing disorders and new alterations. The final consequences are reflected fundamentally as abnormal mineral metabolism (hypercalcemia, hypophosphatemia) and bone alterations [high or low bone turnover disease (as fibrous osteitis or adynamic bone disease), an eventual compromise of bone mineralization, decrease bone mineral density and bone fractures]. The major cause of post-transplantation hypercalcemia is the persistence of severe secondary hyperparathyroidism, and treatment options include calcimimetics or parathyroidectomy. On turn, hypophosphatemia is caused by both the persistence of high blood levels of PTH and/or high blood levels of FGF23, with its correction being very difficult to achieve. The most frequent bone morphology alteration is low bone turnover disease, while high-turnover osteopathy decreases in frequency after transplantation. Although the pathogenic mechanisms of these abnormalities have not been fully clarified, the available evidence suggests that there are a number of factors that play a very important role, such as immunosuppressive treatment, persistently high levels of PTH, vitamin D deficiency and hypophosphatemia. Fracture risk is four-fold higher in transplanted patients compared to general population. The most relevant risk factors for fracture in the kidney transplant population are diabetes mellitus, female sex, advanced age (especially > 65 years), dialysis vintage, high PTH levels and low phosphate levels, osteoporosis, pre-transplant stress fracture and high doses or prolonged steroids therapy. Treatment alternatives for CKD-MBD after transplantation include minimization of corticosteroids, use of calcium and vitamin D supplements, antiresorptives (bisphosphonates or Denosumab) and osteoformers (synthetic parathyroid hormone). As both mineral metabolism and bone disorders lead to increased morbidity and mortality, the presence of these changes after transplantation has to be prevented (if possible), minimized, diagnosed, and treated as soon as possible.

Osteoporosis, densidad mineral ósea y complejo CKD-MBD (I): consideraciones diagnósticas / Osteoporosis, bone mineral density and CKD-MBD complex (I): Diagnostic considerations

Osteoporosis (OP) y enfermedad renal crónica (ERC) influyen de manera independiente en la salud ósea y cardiovascular. Un número significativo de pacientes con ERC, especialmente desde estadios 3a a 5D, presentan una disminución significativa de la densidad mineral ósea condicionando un alto riesgo de fractura y un incremento importante de la morbimortalidad asociada. Independientemente de la OP clásica asociada a edad y/o sexo, las propiedades mecánicas del hueso se encuentran afectadas adicionalmente por factores intrínsecos a la ERC ("OP urémica"). En la primera parte de esta revisión, analizaremos conceptos generales sobre densidad mineral ósea, OP y fracturas, en gran parte infravalorados hasta ahora por los nefrólogos debido a la falta de evidencias y a las dificultades diagnósticas en el contexto de la ERC. Actualmente se ha demostrado que una densidad mineral ósea disminuida es realmente predictiva del riesgo de fracturas en pacientes con ERC, aunque no permite distinguir entre las causas que la originan (hiperparatiroidismo, enfermedad adinámica del hueso y/o osteoporosis senil, etc.). Por ello, en la segunda parte analizaremos las implicaciones terapéuticas en distintos estadios de la ERC. En cualquier caso, la valoración individualizada de los factores mayores y menores del riesgo de fractura, la cuantificación de dicho riesgo (i.e. con el uso de herramientas como el FRAX(R)) y las indicaciones potenciales de densitometría en pacientes con ERC podrían constituir un primer paso importante en espera de nuevas guías clínicas basadas en estudios aleatorizados que no excluyan a pacientes con ERC, evitando mientras tanto nihilismo terapéutico en un área de creciente importancia

Osteoporosis (OP) and chronic kidney disease (CKD) independently influence bone and cardiovascular health. A considerable number of patients with CKD, especially those with stages 3a to 5D, have a significantly reduced bone mineral density leading to a high risk of fracture and a significant increase in associated morbidity and mortality. Independently of classic OP related to age and/or gender, the mechanical properties of bone are also affected by inherent risk factors for CKD ("uraemic OP"). In the first part of this review, we will analyse the general concepts regarding bone mineral density, OP and fractures, which have been largely undervalued until now by nephrologists due to the lack of evidence and diagnostic difficulties in the context of CKD. It has now been proven that a reduced bone mineral density is highly predictive of fracture risk in CKD patients, although it does not allow a distinction to be made between the causes which generate it (hyperparathyroidism, adynamic bone disease and/or senile osteoporosis, etc.). Therefore, in the second part, we will analyse the therapeutic indications in different CKD stages. In any case, the individual assessment of factors which represent a higher or lower risk of fracture, the quantification of this risk (i.e. using tools such as FRAX(R)) and the potential indications for densitometry in patients with CKD could represent an important first step pending new clinical guidelines based on randomised studies which do not exclude CKD patients, all the while avoiding therapeutic nihilism in an area of growing importance

Osteoporosis, bone mineral density and CKD-MBD complex (I): Diagnostic considerations. / Osteoporosis, densidad mineral ósea y complejo CKD-MBD (I): consideraciones diagnósticas.

Osteoporosis (OP) and chronic kidney disease (CKD) independently influence bone and cardiovascular health. A considerable number of patients with CKD, especially those with stages 3a to 5D, have a significantly reduced bone mineral density leading to a high risk of fracture and a significant increase in associated morbidity and mortality. Independently of classic OP related to age and/or gender, the mechanical properties of bone are also affected by inherent risk factors for CKD ("uraemic OP"). In the first part of this review, we will analyse the general concepts regarding bone mineral density, OP and fractures, which have been largely undervalued until now by nephrologists due to the lack of evidence and diagnostic difficulties in the context of CKD. It has now been proven that a reduced bone mineral density is highly predictive of fracture risk in CKD patients, although it does not allow a distinction to be made between the causes which generate it (hyperparathyroidism, adynamic bone disease and/or senile osteoporosis, etc.). Therefore, in the second part, we will analyse the therapeutic indications in different CKD stages. In any case, the individual assessment of factors which represent a higher or lower risk of fracture, the quantification of this risk (i.e. using tools such as FRAX®) and the potential indications for densitometry in patients with CKD could represent an important first step pending new clinical guidelines based on randomised studies which do not exclude CKD patients, all the while avoiding therapeutic nihilism in an area of growing importance.

Fabry Nephropathy: An Evidence-Based Narrative Review.

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options.