Konosuke Konishi

The influence of antecedent renal disease on pregnancy

The influence of antecedent renal disease on pregnancy was studied retrospectively in 72 women with various renal diseases that had been proved by biopsy. Among 105 pregnancies studied, normal deliveries were observed in 74 (71%), abnormal deliveries with live infants in 14 (13%), fetal or neonatal deaths in 11 (10%), and spontaneous abortions in six (6%). The incidence of normal delivery, as well as that of live births, was the highest in the cases of membranous glomerulonephritis, but there was no obvious difference in the incidence among IgA nephropathy and non-IgA proliferative glomerulonephritis. Cases in which there were tubulointerstitial changes of the cortical area or arteriosclerosis in biopsy specimens and cases that included hypertension (greater than 140/90 mm Hg) or decreased renal function (glomerular filtration rate, less than 70 ml/min) were clearly associated with an unfavorable outcome in delivery. It was concluded that assessment of the advisability of pregnancy in nephritic women should be made on the basis of a combination of the clinical and histologic parameters.

Case Report: Hypophosphatemic Osteomalacia in von Recklinghausen Neurofibromatosis

Skeletal lesions are not uncommon in von Recklinghausen neurofibromatosis. Most of them are considered to be dysplastic in nature. Association of osteomalacia or rickets with neurofibromatosis has been documented only rarely. Reported herein is a 40-year-old woman with known von Recklinghausen neurofibromatosis who presented with bone pain, multiple pseudofractures, marked increase in osteoid by bone biopsy, and hypophosphatemia with renal phosphate wasting. Treatment with oral phosphate and vitamin D was effective. A survey of the literature revealed that 34 similar cases have been reported in the past. Although the exact pathogenetic mechanism remains to be determined, osteomalacia in neurofibromatosis appears to be distinct from more common dysplastic skeletal affections of this disease, being characterized by later onset in adulthood as a rule, renal phosphate loss with hypophosphatemia, multiple pseudofractures in typical cases, and response to treatment with pharmacological dose of vitamin D with or without phosphate supplement.

Significance of Tubulointerstitial Lesions in Biopsy Specimens of Glomerulonephritic Patients

To evaluate the significance of tubulointerstitial lesions in the cortical area of renal biopsy specimens, clinicopathological studies were performed on 101 cases of IgA nephropathy, 31 cases of IgA-negative (non-IgA) proliferative glomerulonephritis and 75 cases of idiopathic membranous glomerulonephritis. The degree of tubulointerstitial lesions was assessed semiquantitatively by light microscopic observation and was correlated with the several histopathological and clinical parameters at biopsy, as well as with status at final follow-up (average follow-up period: 72 months). In these three types of glomerulonephritis, the degree of tubulointerstitial lesions in the cortical area was clearly correlated with the severity of glomerular injury, the prevalence of segmental sclerosis, global sclerosis, arteriolosclerosis, decreased renal function (GFR less than 70 ml/min) and hypertension (greater than 150/90 mm Hg) at the time of biopsy. The prevalence of stable renal function at final follow-up was statistically higher in the cases without tubulointerstitial lesions or with those whose lesions included less than 20% of the cortical area. From the above data, it was concluded that a semiquantitative evaluation of tubulointerstitial lesions in the cortex would reflect the severity of glomerular injury and also contribute to the assessment of prognosis in such primary glomerulonephritic patients.

SQ 14, 225 attenuates the vascular response to norepinephrine in the rat mesenteric arteries

Abstract SQ 14, 225, a new angiotensin-converting enzyme inhibitor, attenuated the vascular contraction induced by norepinephrine in the perfused rat mesenteric vascular bed, while SQ 20, 881, an another converting enzyme inhibitor, did not have any effect on the vascular reactivity. Furthermore, this effect of SQ 14, 225 was not altered in the presence of bradykinin or angiotensin II in the perfusate. These results suggest that SQ 14, 225 may have a direct antihypertensive effect which is not mediated by the inhibition of angiotensin-converting enzyme.

Association of a Novel 3-Amino Acid Deletion Mutation of Apolipoprotein E (Apo E Tokyo) with Lipoprotein Glomerulopathy

Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by abnormal lipoprotein deposition in the glomeruli, dysbetalipoproteinemia, and a high level of plasma apolipoprotein (apo) E. We identified a novel apo E mutation in a 56-year-old Japanese male with LPG. Although the plasma cholesterol and triglyceride levels were normal, the levels of intermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/dl (0.336 mmol/l; 4.2±2.9 mg/dl, mean ± SD, in 12 normolipidemic controls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual apo E phenotype (E1/3). Apo E genotyping using DNA digested by a restriction enzyme (HhaI) identified a 66-bp fragment which was not seen with any of the common alleles. Sequence analysis of the amplified genomic DNA fragments showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino acid deletion (residues 141–143). This novel mutation involves the region of the apo E molecule known to be critically involved in binding to its receptor, and this may well transform the apo E molecule, an inefficient ligand, to its receptor(s). How this mutations causes glomerular damage remains to be determined.

Central and peripheral effects of bradykinin and prostaglandin E2 on blood pressure in conscious rats

SummaryBradykinin or prostaglandin E2 (PGE2), when injected intravenously, decreased blood pressure of conscious rats in a dose-dependent manner, while intracerebroventricular injections of bradykinin or PGE2 caused a dose-dependent increase in blood pressure. SQ 14,225, an inhibitor of angiotensin converting enzyme, potentiated the central pressor or peripheral depressor effect of bradykinin. Indomethacin, an inhibitor of prostaglandin synthesis, almost completely inhibited the central pressor effect of bradykinin when injected intraventricularly. Indomenthacin, when injected intravenously, failed to inhibit the peripheral depressor effect of bradykinin, whereas it significantly attenuated the peripheral depressor effect of bradykinin when the angiotensin converting enzyme was inhibited with SQ14,225. These results suggest that the central pressor effect of bradykinin is mainly mediated by the synthesis of prostaglandins in the central nervous system, while only a small fraction of peripheral depressor effect of bradykinin is, at least in conscious rats, mediated by the synthesis of prostaglandins in the systemic circulation.

Hypokalemia and prostaglandin overproduction in Bartter's syndrome

In 2 adult patients with Bartters syndrome, in whom chloride reabsorption at the diluting segment of the nephron was markedly reduced, serum potassium concentration could be improved with oral administration of a large amount of potassium chloride. In both cases, improvement of serum potassium levels with oral potassium load resulted in an increase in plasma renin activity (PRA) and plasma aldosterone concentration (PAC), a decrease in urinary excretion of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), and an improvement of pressor responsiveness to angiotensin II and norepinephrine. Treatment with indomethacin also improved the pressor responsiveness to angiotensin II and norepinephrine, but this occurred in association with a decrease in PRA, PAC and urinary excretion of PGE2 and PGF2 alpha. These results indicated that an event at the renal tubular level leading to potassium depletion is the most proximal pathogenetic defect in Bartters syndrome, and that this in turn contributes to excessive prostaglandin production leading further to the decreased pressor responsiveness to vasoactive substances.

Acute interstitial nephritis associated with ulcerative colitis.

Although drugs used in inflammatory bowel diseases (IBD) cause renal injury, glomerulopathies may also accompany IBD. We report a case with the rare association of ulcerative colitis (UC) and acute progressive interstitial nephritis. Although the kidney is acknowledged as a target organ for injury as a result of drug nephrotoxicity, our findings lend support to the novel recognition that the deranged autoimmune system emerging in UC causes interstitial nephritis as an extraintestinal manifestation. Overt renal failure due to interstitial nephritis has rarely been reported in UC patients. The case presented here therefore provides novel information on UC-associated nephropathy.

A case of atypical POEMS syndrome without polyneuropathy

POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M‐protein, Skin changes) syndrome is a rare hematological disease associated with overproduction of pro‐inflammatory cytokines. Under the current nomenclature and diagnostic criteria for POEMS syndrome, the presence of characteristic polyneuropathy is required for diagnosis. We report a 43‐year‐old Japanese woman with organomegaly, endocrinopathy, M‐protein, skin lesions, as well as typical renal lesions and sclerotic bone lesions. Of note, neurological examinations and peripheral nerve conduction tests were normal in this patient. In view of the overwhelming number of otherwise characteristic signs and symptoms, we made a provisional diagnosis of ‘atypical POEMS syndrome without polyneuropathy’. If further similar cases are reported in the future, reconsideration of the nomenclature and/or diagnostic criteria for POEMS syndrome may be required.

MPO-ANCA associated crescentic glomerulonephritis with numerous immune complexes: case report.

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (CGN) is a major cause of rapidly progressive glomerulonephritis (RPGN). ANCA-associated CGN is generally classified into pauci-immune RPGN, in which there are few or no immune complexes.Case PresentationA 78-year-old man presented with RPGN after a 7-year course of chronic proteinuria and hematuria with stable renal function. A blood examination showed a high titer of myeloperoxidase (MPO)-ANCA. A renal biopsy showed crescentic glomerulonephritis with abundant subepithelial, intramenbranous and subendothelial deposits by electron microscopy, leading to the diagnosis of ANCA-associated CGN superimposed on type 3 membranoproliferative glomerulonephritis (MPGN).ConclusionsThis case is unique in that type 3 MPGN and MPO-ANCA-associated CGN coexisted, and no similar case has been reported to date. Because ANCA-associated CGN has a predilection for elderly individuals and primary type 3 MPGN is rarely seen in this age group, coincidental existence appears less likely. This case may confer valuable information regarding the link between immune complex and ANCA-associated CGN.