Impact of focal segmental glomerulosclerosis over the past decade.

OBJECTIVE: This is a study on the demographics and clinical outcomes including the response to therapy of patients with focal segmental glomerulosclerosis (FSGS) over the past decade. MATERIALS AND METHODS: All histologically proven FSGS cases diagnosed between 2008 and 2018 were analyzed for their clinical, laboratory, and histological characteristics including treatment that could influence the disease progression and renal outcome of these patients. We used the Columbia Classification for FSGS for the renal biopsy. RESULTS: There were two subgroups of FSGS patients; those with nephrotic syndrome and those without nephrotic syndrome. Patients with FSGS with non-nephrotic syndrome had poorer survival rates compared to the nephrotic group. For those without nephrotic syndrome, the indices responsible for progression involved more tubular and blood vessel lesions in addition to glomerular pathology compared to those with nephrotic syndrome. Patients with FSGS with nephrotic syndrome responded to immunosuppressants more favorably compared to the non-nephrotic group, though both groups responded with decreasing proteinuria. The nephrotic group had a better 10-year long-term survival rate of 92 vs. 72% for the non-nephrotic group (log-rank 0.002). The 10-year survival for the whole group of FSGS patients was 64%. CONCLUSION: Our data suggest that in FSGS, one of the significant components of the disease is the vascular and tubular damage, apart from the underlying glomerular pathology, resulting in varying responses to therapy, and the difference is reflected in inherently poorer response to immunosuppressant therapy in those without nephrotic syndrome as opposed to those with nephrotic syndrome, who responded to immunosuppressant therapy (IST) with stabilization of renal function and had less blood vessel and tubular lesions.

Prevalence and outcomes associated with hypocalcaemia and hypercalcaemia among pre-dialysis chronic kidney disease patients with mineral and bone disorder.

Introduction: Chronic kidney disease-mineral and bone disease (CKD-MBD) is a complication of chronic kidney disease (CKD) involving derangements in serum calcium and phosphate. This study aims to evaluate hypo- and hypercalcaemia and their associated outcomes among pre-dialysis CKD patients. Methods: A retrospective cohort study was performed and included all adult CKD stage 4-stage 5 patients who were on treatment for CKD-MBD between 2016 and 2017. Each patient was followed up for 3 years. Hypo- and hypercalcaemia were defined as serum corrected calcium (Ca2+) <2.10 and >2.46 mmol/L, respectively. Outcomes evaluated included all-cause mortality and cardiovascular events. Multivariate Cox regression analysis was done to evaluate the association of hypocalcaemia and/or hypercalcaemia with the clinical outcomes. Severity of hypocalcaemia episode was classified as 'mild' (Ca2+: between 1.90 and 2.10 mmol/L) and 'severe' (Ca2+: <1.90 mmol/L). Severity of hypercalcaemia was classified as 'mild' (Ca2+: between 2.47 and 3.00 mmol/L), moderate (Ca2+: between 3.01 and 3.50 mmol/L) and severe (Ca2+: >3.50 mmol/L). Results: Of the 400 patients, 169 (42.2%) and 94 (23.5%) patients experienced hypocalcaemia and hypercalcaemia, respectively. Severe hypocalcaemia was more prevalent in CKD stage 5 compared to CKD stage 4 (96 [40.5%] vs. 36 [25.9%], P = 0.004). Results from multivariate analyses after adjustment showed that hypocalcaemia and/or hypercalcaemia were not associated with all-cause mortality (P > 0.05) or the occurrence of cardiovascular events (P > 0.05). Conclusion: Hypocalcaemia and hypercalcaemia episodes were prevalent among pre-dialysis CKD patients. Studies with longer follow-up durations are required to assess the effects of calcium derangements on clinical outcomes.

Hungry bone syndrome after parathyroidectomy in end-stage renal disease patients: review of an alkaline phosphatase-based treatment protocol.

AIM: Hyperparathyroidism in chronic kidney disease-mineral and bone disorder is associated with significant morbidity and mortality. Parathyroidectomy is widely carried out as treatment despite complications such as hypocalcaemia post-surgery. Our centre has been using an ALP-based protocol to replace calcium postoperatively to prevent hypocalcaemia. We aim to describe and audit our calcium replacement protocol post-parathyroidectomy METHODS: We, retrospectively, analyse 167 end-stage kidney disease patients who had parathyroidectomy with auto-implantation in Singapore General Hospital between January 2008 and December 2013. Their calcium replacement postoperatively was initiated upon patient arrival back in ward on the same day of surgery based on their pre-op ALP prior to occurrence of hypocalcaemia. Patient demographics, surgical and laboratory parameters were reviewed from medical records. Changes in calcium postoperatively were reported to look for incidence of calcium derangement. RESULTS: Mean calcium levels between pre-operation day and post-operation day 7 ranged from 2.31 to 2.70 mmol/L. Decline in serum calcium was common in all patients prior to starting calcium replacement. Eighteen patients (10.9%) experienced hypocalcaemia immediately post-operation prior to commencement of IV calcium replacement. Patients with immediate post-operation hypocalcaemia had lower pre-operation calcium but higher pre-operation alkaline phosphatase (ALP) and pre-operation intact parathyroid hormone. Hypercalcaemia is common likely from aggressive IV calcium replacement using the protocol. The average length of stay for patients prior to calcium stabilization and discharge was 9 days. CONCLUSION: Implementation of an ALP-based prophylactic calcium replacement protocol with daily serum calcium monitoring can ameliorate severe hypocalcaemia post-parathyroidectomy.

Secondary and Tertiary Hyperparathyroidism in Chronic Kidney Disease: An Endocrine and Renal Perspective.

Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely defined and understood. During the long course of chronic renal failure, SHP can also transform sometimes into the hypercalcemic state characterized by quasi-autonomous production of Parathyroid Hormone from the parathyroid glands: a disorder that is termed Tertiary Hyperparathyroidism. The clinical consequences of SHP in CKD are protean, encompassing bone and mineral abnormalities but as recently identified, also several metabolic and cardiovascular problems, the most important of which is vascular calcification. There have been several advances in the therapeutic armamentarium available for the treatment of SHP, though clear demonstration of a benefit regarding major clinical outcomes with any of the new agents is still lacking. This narrative review summarizes the current understanding about this disorder and highlights some of the recent research on the subject.

The effect of parathyroidectomy on patients' symptoms in tertiary hyperparathyroidism.

BACKGROUND: The efficacy of parathyroidectomy for primary and secondary hyperparathyroidism is well-established but evidence in tertiary hyperparathyroidism is lacking. We examined parathyroidectomy's effect in tertiary hyperparathyroidism. METHODS: Patients with tertiary hyperparathyroidism who underwent parathyroidectomy were followed up for 12 months. A modification of the 13-item parathyroid symptoms list developed by Pasieka was administered at 0, 1, 3, 6, and 12 months post-surgery. We also examined if preoperative factors would predict symptom improvement post-surgery. RESULTS: Ninety-one patients were included. Survey response rates at 1, 3, 6, and 12 months post-surgery were 97.8%, 90.1%, 82.4%, and 80.2%, respectively. Mean preoperative Pasieka parathyroid score (PSS) was 6.3 ± 2.7. At first month, PSS decreased to 2.9 ± 2.0 (P < .001) and was sustained at 3, 6, and 12 months (2.7 ± 2.1, P < .001, 2.3 ± 1.6, P < .001 and 3.4 ± 2.5, P < .001). The degree of PSS reduction at 1-month post-parathyroidectomy correlated strongly with preoperative symptom severity (Pearson's coefficient: 0.690, P < .001). CONCLUSIONS: Parathyroid symptoms unequivocally improve post-parathyroidectomy. The greatest degree of improvement was observed in early postoperative period up to 6 months.

Metastatic pulmonary calcification: Experience from a single center in Singapore.

Metastatic pulmonary calcification (MPC) was seen in 79% of patients with end-stage renal disease (ESRD) during autopsy. However, it is not commonly diagnosed in vivo. Its pathogenesis is not fully understood. We report a retrospective series of 5 cases of MPC from a single center in Singapore. MPC were diagnosed using radiological or histological features. Mean onset of MPC from diagnosis of ESRD was 22.6 ± 3.1 years. One patient remains asymptomatic. Four patients died, one was related to MPC. All patients had calcifications at the lung apices on radiological studies. Three patients with MPC were diagnosed based on radiological features while 2 had histological features. Four patients underwent parathyroidectomy without radiological changes before parathyroidectomy. Median intact parathyroid hormone of this series was 5.6 pmol/L (IQR 1.3-139.4), alkaline phosphatase 74 U/L (IQR 62-461), calcium 2.10 mmol/L (IQR 1.85-2.40), and phosphate 1.30 mmol/L (IQR 0.87-1.63). The observed low iPTH suggests that MPC might occur in low iPTH. Our case series showed MPC might occur in low iPTH after parathyroidectomy, in contrast to existing literature that suggests MPC is diagnosed in patients with elevated iPTH. Parathyroidectomy does not prevent MPC.

Prevalence and risk factors for hypercalcemia among non-dialysis patients with chronic kidney disease-mineral and bone disorder.

PURPOSE: To examine the prevalence and risk factors for hypercalcemia among non-dialysis chronic kidney disease (CKD) patients with mineral and bone disorder (MBD). METHODS: A retrospective cohort study was conducted in Singapore General Hospital, involving all CKD stage 4 and 5 pre-dialysis patients who were on treatment for MBD in June 2016. Each patient was followed up for 1 year and screened for hypercalcemia episodes. Mild, moderate and severe hypercalcemia were defined as corrected calcium of 2.47-3.00, 3.01-3.50 and ≥ 3.51 mmol/l respectively. Patients who were on dialysis, post-renal transplant, post-parathyroidectomy or had no calcium levels taken during the study period were excluded. Details related to patients' clinical information and hypercalcemia episodes were collected. Multivariate logistic regression analysis was performed to evaluate risk factors for hypercalcemia. RESULTS: Of 557 patients, 75 (13.4%) patients developed hypercalcemia. There were 120 (97.6%) mild and 3 (2.4%) moderate hypercalcemia episodes. The daily elemental calcium intake from phosphate binders and usage of vitamin D analogues did not differ between patients with and without hypercalcemia (p > 0.05). After adjusting for covariates, lower baseline iPTH level [odds ratio (OR) 0.96, 95% CI 0.93-0.99], history of hypercalcemia in past 1 year (OR 11.11, 95% CI 3.36-36.75) and immobility (OR 3.34, 95% CI 1.34-8.40) were associated with increased hypercalcemia risk. CONCLUSION: Hypercalcemia affects a significant proportion of pre-dialysis patients with MBD. More studies should be undertaken to evaluate other risk factors associated with hypercalcemia.

Unusual cause of hypercalcaemia in end stage renal failure patients.

Immobility-induced hypercalcaemia is rarely considered in patients on dialysis and is a challenging diagnosis to make. This is especially so due to the lack of biomarkers as well as the notion that calcium metabolism is mostly related to chronic kidney disease-metabolic bone disorder due to the role of iPTH. We present two cases of our dialysis patients, who were clinically unwell from hypercalcemia. We were initially uncertain of the cause of hypercalcemia as despite our attempts to adjust treatment based on their biochemical findings, we were unable to correct the hypercalcemia. We did not have appropriate bone turnover markers to guide us and out of desperation, anti-resorptives-calcitonin and bisphosphonate were given with good clinical response. We concluded that the hypercalcemia was related to immobility-induced hypercalcemia and the inappropriately low iPTH was a red herring. Immobility-induced hypercalcaemia should be considered in patients with end stage renal failure on renal replacement therapy, especially in those with recent and significant immobility. In these patients, pamidronate can be considered should the hypercalcaemia persist.