Clinical features and hyperplastic patterns of parathyroid glands in hemodialysis patients with advanced secondary hyperparathyroidism refractory to maxacalcitol treatment and required parathyroidectomy.

We have previously suggested that when parathyroid glands progress to nodular hyperplasia, secondary hyperparathyroidism (2HPT) may be refractory to medical treatments, including treatment with Maxacalcitol (OCT). In the present study we evaluated the clinical features and hyperplastic patterns of parathyroid glands in patients who underwent parathyroidectomy (PTx) after being withdrawn from OCT. One hundred and eighty-seven advanced 2HPT patients who had been withdrawn from OCT and required PTx were enrolled. At the start of OCT treatment, the patients had a mean age of 55.3 years and had been receiving hemodialysis (HD) for a mean period of 149 months. At the start of OCT treatment and at PTx, the mean intact PTH (i-PTH) levels were 772.8 +/- 446.0 and 855.5 +/- 420.5 pg/mL, respectively. The main reasons for withdrawal of OCT treatment were persistently high PTH (n = 148), hypercalcemia (n = 79), hyperphosphatemia (n = 65), and progressive symptoms (n = 60). We classified the parathyroid glands by hyperplastic pattern into four categories: diffuse hyperplastic gland (D), early nodularity in diffuse hyperplastic gland (EN), nodular hyperplastic gland (N), and single nodular gland (SN). The mean total excised gland weight was 2592.6 mg. Out of a total of 706 glands, 118 were classified as D, 66 as EN, 436 as N, and 86 as SN. All patients had at least one nodular hyperplastic gland or single nodular gland. The mean number of nodular hyperplastic glands and/or single nodular glands was 2.9. All hemodialysis patients with advanced OCT-refractory 2HPT who underwent PTx had at least one nodular hyperplastic gland or single nodular gland.

Circadian blood pressure rhythm is disturbed by nephrectomy.

We recently illustrated a close relationship between glomerular filtration rate and circadian rhythm of blood pressure (BP) in patients with chronic kidney disease. However, it remains undetermined from such cross-sectional findings which occurs first, the loss of kidney function or the lack of nocturnal BP fall. In the present study, we examined whether circadian rhythm of BP is affected by unilateral nephrectomy for kidney donation to clarify this important issue. Fifteen healthy subjects (4 men, 11 women; aged 33 to 65 years; mean age 55 +/- 2 years) who underwent unilateral nephrectomy for kidney donation were studied. Ambulatory BP was monitored for 24 h, while serum and urinary samples were collected to estimate creatinine clearance before and on the 8th day after nephrectomy. Then, changes in the night/day ratios of mean arterial BP were analyzed in relation to the decrease in 24-h creatinine clearance as a marker of glomerular filtration rate by nephrectomy. Creatinine clearance was reduced by 29% in average from 84 +/- 6 to 60 +/- 4 ml/min by nephrectomy, while 24-h mean arterial BP values were 91 +/- 3 and 94 +/- 4 mmHg (p=0.08) before and after nephrectomy. Although mean BP (daytime, nighttime or night/day ratio) was not altered significantly by nephrectomy, the decrease in creatinine clearance was positively correlated with the increase in the night/ day ratio of mean BP (r=0.61, p=0.017). The decrease in creatinine clearance was not correlated with changes in either 24-h, daytime or nighttime mean BP. Our results suggest that unilateral nephrectomy disturbs the circadian rhythm of BP as a function of renal dysfunction without affecting absolute levels of BP. Non-dipping of BP seems the consequence of the loss of renal function, rather than the cause.

[Two patients with hyperparathyroidism which was progressive for more than ten years after successful kidney transplantation].

It is well known that in some patients advanced renal hyperparathyroidism (HPT) persists after successful kidney transplantation (RTx) and in those patients parathyroidectomy is required usually within one year after RTx. We experienced two patients with advanced renal HPT which released after successful RTx and parathyroidectomy was performed in more than 10 years after RTx, even their kidney function was well-preserved. Hypercalcemia was gradually progressive for ten years after RTx and enlarged parathyroid glands were detected by image diagnosis. We performed parathyroidectomy and HPT was dramatically improved. It is possible that primary HPT occurred de novo after RTx or renal HPT was progressive. We evaluated those possibility based on histopathological findings dramatically improved of removed parathyroid glands.

[Usefulness of power Doppler ultrasonography for the diagnosis of autoinfarction of parathyroid gland in secondary hyperparathyroidism].

Spontaneous remission due to parathyroid infarction of secondary hyperparathyroidism is rare compared with that of primary hyperparathyroidism, probably because several glands are enlarged in secondary hyperparathyroidism. Lately, neck ultrasound examination has become a more beneficial and specific method for the diagnosis of enlarged parathyroid glands in contrast to classic diagnostic techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy. However, the diagnosis of parathyroid infarction reported in previous studies was often based on CT, MRI and scintigraphy findings and there are few studies that reported such diagnosis by urgent power Doppler ultrasonography of the neck. Here we present a hemodialysis patient with autoinfarction of the left parathyroid gland diagnosed by urgent power Doppler ultrasonography of the neck.

Complement fragment C4d deposition in peritubular capillaries in acute humoral rejection after ABO blood group-incompatible human kidney transplantation.

BACKGROUND: Acute humoral rejection (AHR) is the most important risk factor for early graft loss in ABO-incompatible (ABO-i) kidney transplantation (RTx). The pathogenesis and diagnostic criteria for AHR after ABO-i RTx remain unclear. Complement fragment C4d deposition in peritubular capillaries (PTC), which is a sensitive indicator for activation of the classical complement pathway, was studied to establish the pathologic diagnostic indicator of AHR. METHODS: Forty-four graft biopsy specimens from 19 patients with ABO-i living donors were analyzed within 90 days after RTx. Nineteen biopsy specimens with acute rejection after ABO-compatible (ABO-c) living-related RTx were used as controls. Diffuse and bright C4d deposition in PTC was considered significantly positive. RESULTS: All of 8 recipients with AHR showed significantly positive C4d in PTC in the ABO-i group, but 9 of 11 recipients without AHR were negative. In the ABO-c RTx group, 16 of 19 recipients were negative for C4d in PTC. The prevalence of C4d in PTC was significantly higher in ABO-i RTx (P<0.05). CONCLUSIONS: C4d deposition is valuable as a specific and sensitive indicator for AHR, even of mild severity, in ABO-i RTx.

Diabetes mellitus after transplant: relationship to pretransplant glucose metabolism and tacrolimus or cyclosporine A-based therapy.

OBJECTIVE: The purpose of this study was to identify pretransplantation and posttransplantation indicators for the development of diabetes mellitus in the first 2 months after renal transplantation and to examine the influence of a cyclosporine A (CsA)-based versus a tacrolimus-based immunosuppressive regimen on these risk factors. METHODS: Key variables associated with the development of posttransplant diabetes mellitus (PTDM) in the first 2 months after transplantation were assessed in 48 patients who underwent living-related renal transplantation and who were treated with a CsA-based or a tacrolimus-based immunosuppressive regimen. The insulinogenic index (I Index) and glucose infusion rate (GIR) were measures of insulin secretion and insulin sensitivity, respectively. RESULTS: Eight patients developed PTDM. I Index (odds ratio, 0.000384) and GIR (odds ratio, 0.349) were significant risk factors for PTDM development. The cumulative steroid dose had a borderline association. PTDM developed in 4 of 28 CsA-treated patients and in 4 of 20 tacrolimus-treated patients. CsA therapy increased the mean I Index from 0.713+/-0.071 preoperatively to 1.130+/-0.140 postoperatively (P<0.01), whereas in tacrolimus-treated patients, I Index remained unchanged (1.09+/-0.264 preoperatively and 0.949+/-0.296 postoperatively; P=not significant). Age, duration of pretransplant dialysis, and body mass index did not predict PTDM development. All eight patients with PTDM had hypertension. CONCLUSIONS: Pre- and posttransplant abnormalities of insulin secretion and sensitivity are significant predictors of PTDM. Corticosteroid cumulative dose may affect the incidence of PTDM during the first 2 months after transplantation. CsA treatment increases insulin secretion in patients with a high pretransplant risk of PTDM.

Infarction of mediastinal parathyroid gland causing spontaneous remission of secondary hyperparathyroidism.

Secondary hyperparathyroidism is a serious complication in long-term hemodialysis patients. The authors report on 2 patients on long-term hemodialysis who suffered from persistent secondary hyperparathyroidism due to missed mediastinal parathyroid gland after total parathyroidectomy with forearm autograft. Reoperation was planned. In both cases, severe hypocalcemia suddenly developed; serum parathyroid hormone (PTH) level decreased markedly after this episode. The serum calcium level increased gradually in response to administration of vitamin D and calcium carbonate, but serum PTH level remained low. A follow-up computed tomography scan showed that the formerly enlarged mediastinal parathyroid gland was markedly reduced in size. Moreover, a hot spot formerly detected by technetium 99m-MIBI (methoxy-isobutyl-isonitrile) scintigraphy in the mediastinum disappeared after this episode. The authors considered that necrosis of the enlarged ectopic parathyroid gland, probably due to infarction, resulted in hypocalcemia. To the authors' knowledge, this is the first case report of spontaneous mediastinal parathyroid autoinfarction after parathyroidectomy in hemodialysis patients.

Total parathyroidectomy reduces elevated circulating fibroblast growth factor 23 in advanced secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism is a common complication in patients with stage 5 chronic kidney disease (CKD), accelerated by hyperphosphatemia. Fibroblast growth factor 23 (FGF-23), a phosphorus-regulating protein, has key roles in several phosphate-wasting disorders. The aim of this study is to examine the association of advanced secondary hyperparathyroidism with circulating FGF-23 levels. METHODS: Fifteen patients with marked secondary hyperparathyroidism (parathyroid hormone [PTH], 990 +/- 118 pg/mL [ng/L]) were enrolled. All underwent parathyroidectomy with forearm autotransplantation (PTX), and their FGF-23 levels were measured before and after PTX (days 1, 3, 7, and 10) by means of sandwich enzyme-linked immunosorbent assay. RESULTS: Preoperative FGF-23 levels correlated positively with phosphorus (P < 0.05), calcium-phosphorus product (Ca x P; P < 0.0005), and PTH values (P < 0.05). Serum FGF-23 levels decreased time dependently after PTX (P < 0.0005). Both serum phosphorus and Ca x P values decreased similarly after PTX ( P = 0.0001). Furthermore, FGF-23 levels days 1 and 3 correlated linearly with serum phosphorus (P < 0.05; P < 0.005, respectively) and Ca x P values (P < 0.01; P < 0.0001, respectively). CONCLUSION: FGF-23 levels correlate positively with serum phosphorus, Ca x P, and PTH values in patients with advanced secondary hyperparathyroidism. Complete ablation of progressive parathyroid glands reduces circulating FGF-23 levels, simultaneously decreasing serum phosphorus and Ca x P values. These findings suggest that hyperplastic parathyroid glands, together with hyperphosphatemia, affect abnormal FGF-23 metabolism in patients with stage 5 CKD with advanced secondary hyperparathyroidism.

Cardiovascular complications caused by advanced secondary hyperparathyroidism in chronic dialysis patients; special focus on dilated cardiomyopathy.

BACKGROUND: The frequency and prognosis of dilated cardiomyopathy (DCM) caused by secondary hyperparathyroidism (2 degrees HPT) is not known. The purpose of this study was to determine the morbidity of DCM caused by 2 degrees HPT and the efficacy of parathyroidectomy (PTx) in chronic dialysis patients with advanced 2 degrees HPT was analyzed prospectively. METHODS: Between November 2000 and January 2003, 237 dialysis patients who underwent total PTx with forearm autograft at our department were enrolled in this study. Cardiac complications that existed before PTx were examined. Ten patients (4%) had DCM without valvular disease (VD) or ischemic heart disease (IHD). In these 10 patients with DCM before operation, we estimated left ventricular (LV) function at 6 months after PTx, according to echocardiography findings and clinical symptoms. RESULTS: Six months after PTx, left ventricular ejection fraction (LVEF) in these 10 patients was significantly improved, from 31.0 +/- 9.8% before PTx, to 56.8 +/- 13.5% (P = 0.0003), and left ventricular end-diastolic dimension (LVDd) was reduced, from 59.8 +/- 9.7 mm to 46.3 +/- 7.0 mm (P = 0.0014). The symptoms due to DCM and the fall of blood pressure that had occurred during dialysis were clearly improved after PTx. CONCLUSIONS: Advanced 2 degrees HPT can influence LV function, and in patients who suffered from DCM, LV function was dramatically improved by PTx. PTx should be performed immediately in patients with DCM caused by 2 degrees HPT.

Calciphylaxis: a rare complication of patients who required parathyroidectomy for advanced renal hyperparathyroidism.

Calciphylaxis is a relatively rare but life-threatening complication in uremic patients. Clinical findings and prognosis were evaluated in six patients who developed calciphylaxis from a group of 1499 patients who underwent parathyroidectomy (PTx) for advanced renal hyperparathyroidism (HPT) in our department from July 1972 to July 2003. The frequency of calciphylaxis was 0.40% (6/1499). Two patients were women and four were men. The mean age was 50.5 years, and the mean duration of hemodialysis (HD) treatment was 14.0 years. In five of six patients, calciphylaxis was classified as distal type; in one case, as proximal type. In three patients, calciphylaxis was diagnosed at the time for PTx. In two patients, calciphylaxis was identified after PTx, although the serum parathyroid hormone (PTH) level was within the appropriate range for dialysis patients. In two patients, calciphylaxis improved after PTx, but two patients required leg and toe amputations after PTx. In one patient with the proximal type of calciphylaxis, the condition occurred when a high PTH level recurred after the initial PTx. The patient died as a result of a serious infection due to uncontrollable skin ulcers. Calciphylaxis is a rare complication in patients who require PTx for renal HPT. Especially the proximal type has a poor prognosis. High levels of the Ca x P product and/or PTH are risk factors. Therefore, this syndrome should be kept in mind and attention should be paid to reduce risk factors. It is important that PTx being performed at the right time in patients with advanced renal HPT refractory to medical treatment.

Re-operation is frequently required when parathyroid glands remain after initial parathyroidectomy for advanced secondary hyperparathyroidism in uraemic patients.

BACKGROUND: Parathyroidectomy (PTx) is the most successful treatment for advanced secondary hyperparathyroidism (2HPT) not responsive to medical treatment. However, persistent HPT remains problematic after PTx if some glands remain. The clinical course in patients with persistent 2HPT was evaluated to clarify the risk for re-operation after PTx. METHODS: Between March 1981 and December 2001, initial total PTx with forearm autograft were performed in 1156 uraemic patients. Persistent HPT cases were defined as those in which the lowest post-operative intact parathyroid hormone (i-PTH) concentration was >60 pg/ml, and patients were classified into groups A, B and C, with i-PTH concentrations of >or=500, 300-500 and 60-300 pg/ml, respectively. These patients were followed for 7-234 months after PTx. RESULTS: Persistent HPT was identified in 49/1156 patients (4.2%), with nine cases in group A, 10 in group B and 30 in group C. Re-operation was required in 21/49 (42.8%) cases, and in seven of these the last i-PTH concentration was >or=500 pg/ml. All cases in group A required re-operation. In group C, 11/30 (36.7%) patients required re-operation. The missed glands removed at re-operation were supernumerary in 14 cases, and located in the mediastinum in 13 cases. The frequency of advanced HPT and re-operation was not negligible. CONCLUSIONS: To prevent persistent 2HPT, all parathyroid glands must be found and resected during the initial operation. Even if small parathyroid glands remain, there is a risk of progression. Complete PTx is the first treatment choice for advanced 2HPT.

A case report of a renal transplant recipient developing chronic glomerular rejection with a weak antibody against anti-donor T-cell, only detected by flow-cytometry crossmatch.

The pathogenesis of antibody-mediated rejection has been investigated, but the precise mechanism of chronic glomerular rejection remains unclear. We have followed the clinicopathological course of a patient with pre-existing anti-donor antibody only detected by flow-cytometry crossmatch for over 3 years. Glomerular endothelial injuries and peculiar glomerular lesions were noted in biopsy specimen of postoperative year 3; however, both typical chronic vascular rejection lesions and peritubular capillary multilayered lesions were not revealed. We consider that the presence of weak anti-donor antibody leading early onset of acute humoral rejection played a role in the pathogenesis of early onset of chronic transplant glomerulopathy.

Reoperation for renal hyperparathyroidism.

Reoperation for secondary hyperparathyroidism (HPT) due to uremia (2HPT) may be required among patients with persistent renal failure if not all parathyroid glands are removed at the initial operation. Between March 1981 and July 2001, altogether 1,110 patients underwent total parathyroidectomy with forearm autograft for advanced 2HPT in our department. In this study, we evaluated the clinical features of patients who required reoperation and classified them into persistent HPT [the lowest intact parathyroid (PTH) level after initial operation remained higher than 60 pg/ml] and recurrent HPT (the lowest intact PTH level was normalized after surgery but reelevated became high enough to require reoperation). Removal of residual glands was indicated in 30 (2.7%) cases for persistent or recurrent HPT. All remaining glands were detected by preoperative imaging diagnoses. In 44 (4.0%) patients persistent HPT was recognized and in 15 of them (1.4% of all cases) reoperation was required. In 11 cases, the responsible glands were supernumerary ones removed from the mediastinum. In 4 cases, the glands were resected from the neck. In 15 cases (1.4%), reoperation was performed for recurrent HPT when residual glands were left either in the neck or in the thymic tongue. In all but one case, the missed glands were supernumerary. This study reveals that it is often difficult to avoid persistent HPT induced by mediastinal supernumerary glands and recurrent HPT caused by small glands left in the neck. Our findings indicate that patients with uremia should be closely followed considering the possibility that persistent or recurrent HPT may occur after parathyroidectomy.