Unilateral papillary necrosis complicating renal artery stenosis—evidence of activation of the intrarenal renin–angiotensin system?

We report an association between renal artery stenosis and papillary necrosis. We studied three kidneys with renal artery stenosis, two of which showed ipsilateral acute papillary necrosis. In all three cases there had been a sudden fall in perfusion of the ischaemic kidney. In the case with intact papillae, immunostainable renin was normal in amount and distribution, whereas both kidneys with papillary necrosis showed hyperplasia of renin-containing cells, and these were mainly in the JGAs of the juxtamedullary cortex. Since the contralateral kidneys were spared, we suggest that in an ischaemic kidney with hyperplasia of renin-secreting cells in the deep cortex, local activation of the renin-angiotensin system could cause acute papillary necrosis due to vasoconstriction.     

Cellular osmoregulation in the renal papilla

Summary The cells of the renal papilla are subject to extreme variations in extracellular tonicity. To obtain more insight into the mechanisms whereby these cells adapt osmotically to these unique environmental conditions, elements were measured in individual cells of the rat renal papilla in antidiuresis and after prolonged furosemide administration. In antidiuresis cell sodium, chloride and potassium concentrations did not differ fundamentally from those observed in tubule cells exposed to isotonic surroundings such as in proximal tubule cells. The marked fall in extracellular electrolyte concentrations induced by furosemide was paralleled by a far less pronounced decline in intracellular sodium, chloride and potassium concentrations. These data indicate that papillary cells achieve osmoadaptation to widely differing extracellular tonicities mainly by varying the intracellular concentrations of osmotically active substances other than inorganic electrolytes. Since high concentrations of organic osmolytes (sorbitol, inositol, glycerophosphorylcholine and other trimethylamines) have been detected in the papilla and since the tissue contents of these compounds have been shown to vary in parallel with urine osmolality, it may be concluded that metabolically inert, organic osmolytes play a dominant role in the osmoregulation of renal papillary cells.     

Presence and extent of histological tumour necrosis is an adverse prognostic factor in papillary type 1 but not in papillary type 2 renal cell carcinoma

Aims: To date, only limited information is available on the prognostic significance of the presence and extent of histological tumour necrosis with regard to papillary renal cell carcinoma (RCC) types 1 and 2 subclassification. Thus, the aim of this study was to evaluate the prognostic impact of these pathological features on the clinical outcome in papillary subtypes. Methods and results: The influence of histological tumour necrosis on the clinical outcome in 177 patients with papillary RCC was evaluated. For papillary subtype 1, the presence of histological tumour necrosis was an independent negative prognostic factor for disease‐free survival (P = 0.039), and a greater extent of necrosis (>20%) was significantly associated with both poor disease‐free and overall survival (P = 0.033 and P = 0.041, respectively). Regarding papillary subtype 2, neither the presence nor extent of histological tumour necrosis was a statistically significant negative prognostic factor. Conclusion: Our findings suggest that the presence and extent of histological tumour necrosis are independent prognosticators in papillary RCC subtype 1, but not in papillary subtype 2. Thus, previously reported conflicting data regarding the prognostic impact of tumour necrosis in papillary RCC might be explained, in part, by heterogeneous subtypes.     

The possibility of scar formation due to intrarenal reflux in analgesic nephropathy

Summary Using an autopsy case of a 59-year-old man with analgesic nephropathy, papillary necrosis, and nephrolithiasis, it is shown that analgesic nephropathy may be complicated by damage resulting from intrarenal urine reflux. The morphologic alterations characteristic of intrarenal and/or pyelointerstitial reflux are caused by high intrapelvic pressure values during episodes of renal colic. Bacterially infected and possibly also sterile urine is then forced into the interstitium, directly within the papillary defect or indirectly via the tubular system after rupture of the tubule. The result is a severe interstitial process with inflammation, destruction, and scarring.     

Einfluß verschiedener Faktoren auf die Progredienz der Niereninsuffizienz bei Analgetikanephropathie

Summary In a retrospective study of 33 patients the influence of different anamnestic, clinical and laboratory parameters on the progression of renal failure was investigated. The analysis of progression of renal failure was evaluated in terms of a reasonable criterium intuitively suggesting itself which is based on a non-linear fitting of the serum creatinine profile. Follow-up serum creatinine levels showed that renal function became worse in 28 cases, with terminal renal failure developing in 6 cases. In 5 patients significant improvement in kidney function was observed. The variables systolic and diastolic blood pressure, total amount of ingested analgesics, continued abuse and cessation of analgesics, frequency of urinary tract infections and amount of proteinuria had no significant influence on progression of renal failure. However, a strong relationship between the initial serum creatinine level and the progression of renal failure could be established.In conclusion our results indicate that long-term prognosis of analgesic nephropathy mainly depends on early diagnosis.

     

The protective effects of aqueous extract of Carica papaya seeds in paracetamol induced nephrotoxicity in male wistar rats

Background

Oxidative stress plays a crucial role in the development of drug induced nephrotoxicity. The study aimed to determine the nephroprotective and ameliorative effects of Carica papaya seed extract in paracetamol-induced nephrotoxicity in rats.

Objectives

To carry out phytochemical screening of Carica papaya, measure serum urea, creatinine and uric acid and describe the histopathological status of the kidneys in the treated and untreated groups.

Methods

Phytochemical screening of the extract was done. Thirty two adult male Wistar rats were divided into four groups (n= 8 in each group). Group A (control) animals received normal saline for seven days, group B (paracetamol group) received normal saline, and paracetamol single dose on the 8th day. Group C received Carica papaya extract (CPE) 500 mg/kg, and paracetamol on the 8th day, while group D, rats were pretreated with CPE 750 mg/kg/day,and paracetamol administration on the 8th day. Samples of kidney tissue were removed for histopathological examination.

Results

Screening of Carica papaya showed presence of nephroprotective pytochemicals. Paracetamol administration resulted in significant elevation of renal function markers. CPE ameliorated the effect of paracetamol by reducing the markers as well as reversing the paracetamol-induced changes in kidney architecture.

Conclusion

Carica papaya contains nephroprotective phytochemicals and may be useful in preventing kidney damage induced by paracetamol.     

Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats

Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.     

Unsuspected analgesic nephropathy in transitional cell carcinoma of the upper tract: a morphological study

Analgesic nephropathy is known to have a high incidence in Australia where, following the experience in Scandinavia, reports have been published for some time recording the association between analgesic nephropathy and urothelial malignancies. The morbid anatomical features of analgesic nephropathy are now sufficiently well accepted to allow a retrospective study of unselected nephrectomies for transitional cell carcinoma of the renal pelvis and ureter, in order to assess the incidence of analgesic-type changes in this well defined group of malignancies. The records of a large general histopathology department between 1972–1978 were searched and 24 consecutive transitional cell carcinomas in these sites treated by nephrectomy were selected for study. Of these, 21 were suitable for assessment and on review were shown to comprise 11 cases with papillary changes acceptable as analgesic in type and five which were suggestive of early analgesic change. Of these 16, seven were female, only two were known analgesic abusers and five were recorded as consuming analgesics on a regular basis. These findings suggest that analgesics may play a significant role in the pathogenesis of urothelial malignancy in the general population.     

大鼠IgA肾病模型肾脏变化分析

目的探讨IgA肾病(IgA nephropathy,IgAN)大鼠肾小体、肾小囊、肾小球和近端肾小管病理变化。方法将20只SD雌性大鼠随机分成2组,即对照组和IgAN组(n=10)。用免疫荧光、HE染色和体视学方法,测出2组动物肾小体、肾小囊和肾小球体密度、球囊体积比、肾小体数密度、肾小体和肾小球长径、近端肾小管管腔和管壁面积及其比值,比较其差异。结果IgA免疫荧光染色,IgAN组皮质部见较强绿色荧光。与对照组比,IgAN组肾小体体密度增大,肾小囊体密度增大,肾小球体密度减小,球囊比减小,肾小体数密度变化差异无显著性,肾小体长径增大,肾小球长径减小,近端肾小管管腔面积减小,管壁面积增大,腔壁比减小。结论 IgAN大鼠肾小体和肾小囊增大,肾小球减小,近曲小管细胞体积增大,管腔变小。     

乳头状肾细胞癌32例临床病理分析

目的：探讨乳头状肾细胞癌( papillary renal cell carcinoma, PRCC)的临床病理特征、免疫表型、鉴别诊断和预后。方法回顾性分析32例PRCC患者的临床和病理资料,采用免疫组化EnVision法染色,并对患者进行随访。其中21例行根治性肾切除术,11例行肾部分切除术。结果770例肾上皮性肿瘤中32例为PRCC(4.2%)。镜下见PRCC主要由多少不等的乳头状和管状结构组成,被覆单层立方或多层柱状肿瘤细胞,乳头轴心及间质内可见泡沫细胞、砂砾体沉积,部分肿瘤细胞胞质内可见含铁血黄素。Ⅰ型18例,细胞呈立方形,胞质少,嗜碱性,淡染,Fuhrman分级低级别16例;Ⅱ型14例,细胞呈高柱状,胞质丰富,嗜酸性,Fuhrman分级高级别12例。Ⅰ型和Ⅱ型PRCC不同程度地表达vimentin、EMA、CK(AE1/AE3)、CK7、CD10和AMACR,均不表达CK(34βE12)和TFE-3。31例患者获得随访,1例术后肝、肺转移,4个月后死亡,3例术后1年分别出现骨、肺、肝等处转移,2年后死亡;死亡患者中Ⅱ型3例、Ⅰ型1例。其余27例均无瘤生存。高核分级、血管内癌栓、淋巴结转移、高临床分期提示患者预后较差。结论 PRCC国内少见,具有独特的病理形态特征,Ⅱ型PRCC较Ⅰ型患者预后差。 PRCC细胞核分级高、出现肉瘤样成分或有透明细胞癌结构可能提示肿瘤具有侵袭性,预后不良。诊断时需结合病理组织学特征、免疫表型和细胞遗传学分析。     

Primary renal glomus tumor with concurrent papillary renal cell carcinoma and multiple papillary adenomas in a patient with end stage renal disease: a case report and clinicopathologic analysis

Glomus tumors are mesenchymal tumors commonly seen in the extremities, and rarely seen in deep visceral organs. This is due to the lack of glomus bodies in visceral organs. Here, we describe an unusual association between glomus tumor and co-existing papillary renal cell carcinoma, multiple papillary adenomas, and end stage renal disease. We discuss our diagnostic approach and differential diagnoses, along with an extensive review of all reported benign and malignant primary glomus tumors. A 63-year-old male with a known history of a kidney transplant, end-stage renal disease, and previous nephrectomy of his right kidney due to a renal mass (papillary renal cell carcinoma) presented with a renal mass. Microscopic examination showed papillary carcinoma, multiple papillary adenomas, and a small nodule with uniform, round to oval cells. Immunohistochemical work-up revealed the small nodule to be a glomus tumor. Only 28 cases of primary renal glomus tumors have been reported in the literature. Most were discovered incidentally. None of the reported cases have occurred along with other renal tumors. This is the first case of the unusual combination of primary renal glomus tumor arising in the native kidney of a renal transplant patient with concurrent papillary renal cell carcinoma and multiple papillary adenomas (renal adenomatosis). We also explore the possible genetic basis behind this association.     

A comparison of ketamine and paracetamol for preventing remifentanil induced hyperalgesia in patients undergoing total abdominal hysterectomy

Background: The aim of this prospective, randomized, placebo-controlled study was to compare the effects of ketamine and paracetamol on preventing remifentanil induced hyperalgesia.Methods: Ninety patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups to receive (I) either saline infusion; (II) 0.5 mg/kg ketamine iv bolus or (III) 1000 mg iv paracetamol infusion before induction of anesthesia. Until the skin closure, anesthesia was maintained with 0.4 µg/kg/min remifentanil infusion in all groups, additionally Group II received 5 µg/kg/min ketamine infusion. Pressure pain thresholds were measured the day before surgery during the preoperative visit for baseline measurements and repeated postoperatively at 24 and 48 hours (hrs). Pressure pain thresholds were established by digital algometer on three different peri- incisional regions for calculating mean pressure pain threshold values. The visual analogue scale (VAS), sedation scores, total morphine consumption and side effects were assessed postoperatively.Results: Demographic characteristics, duration of surgery and anesthesia were similar in the three groups. Pain thresholds at the incision region were significantly lower at 24 and 48 hrs postoperatively in Group I than the other Groups (p< 0.05). In Group І, pain thresholds were lower compared with preoperative baseline values. Thresholds in Group ІІ and Group ІІІ were higher compared with preoperative baseline values (p< 0.05) The VAS scores at all evaluation times were significantly higher in Group І when compared to Group ІІ and at 2, 4, 6 ,12 hrs were higher in Group I than Group ІІІ (p< 0.05). The morphine consumption was higher in Group ІІІ at 24 and 48 hrs postoperatively (p< 0.05).Conclusion: It was shown that ketamine and paracetamol were both effective in preventing remifentanil induced hyperalgesia.     

Role and regulation of glycerophosphorylcholine in rat renal papilla

Glycerophosphorylcholine (GPC) — an organic solute which is considered to be involved in cellular osmoregulation in the renal medulla — was determined by means of an enzymatic assay in various zones of the rat kidney and in papillary tubule suspensions. In antidiuresis, GPC content in cortex, outer medulla and papillary tip was 0.64, 14.6, and 108.9 mmol/kg fresh weight, respectively. Significant concentrations of GPC could not be detected in the urine or in the peripheral plasma. The sharp increase in GPC concentration from cortex to papillary tip was partially abolished by the induction of diuresis by either waterloading or furosemide. These manoeuvres, however, did not change cortical GPC content. Papillary tubule suspensions prepared from hydrogenic rats contained only slightly less GPC per g protein than whole, papillae from antidiuretic animals. Incubation of tubules over 120 min did not lead to a singnificant loss of GPC which is in accordance with the low activity of GPC degrading enzymes in papillary tissue. The results confirm the intracellular localization of GPC and provide further evidence that this substance plays a substantial role in the osmoregulation of renal papillary cells.     

A study on renal papillary necrosis experimentally produced by the Shwartzman mechanism in rabbits

To produce renal papillary necrosis experimentally by means of the Shwartzman mechanism in rabbits, E. coli endotoxin was injected into the renal pelvis unilaterally through the ureter as a preparative procedure after pretreatment by local administration of alcohol, and the same endotoxin was given again 24 hours later, but intravenously this time via the ear vein, as a provocation. Marked necrosis was produced in the renal papillae, where many intravascular fibrin thrombi were found histologically. Such papillary necrosis was largely prevented by heparin administration, and this lesion was considered to be the univisceral Shwartzman reaction occurring in the renal papillae. The lesion produced in the new experimental system of renal papillary necrosis described here has a good similarity to that of human cases in etiology, pathogenesis and morphology. The present system may therefore be a good model of human renal papillary necrosis, and should be useful for future studies.     

Synchronous chromophobe and papillary renal cell carcinoma. First report and review of the pathogenesis theories

The coexistence of different subtypes of renal cell carcinoma (RCC) within a single kidney is an extremely unusual entity. Presented herein is the case of a 57-year-old man with two RCC of chromophobe and papillary histology. Very few reports in the literature describe double or triple synchronous renal neoplasms. To our knowledge this is the first report of this RCC subtype combination, which might trigger further investigation on the RCC pathogenesis theories.     

Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumour and a comparative genomic hybridization array study of seven cases

Adam J, Couturier J, Molinié V, Vieillefond A & Sibony M
(2011) Histopathology 58, 1064–1071
Clear‐cell papillary renal cell carcinoma: 24 cases of a distinct low‐grade renal tumour and a comparative genomic hybridization array study of seven cases Aims: To report clinicopathological and genomic characteristics of (ccpRCC), a rare, recently characterized renal tumour entity. Methods and results: Twenty‐four renal tumours identified as ccpRCC were collected. Data from comparative genomic hybridization on microarrays (array‐CGH) were obtained for seven of these. Most tumours (58%) occurred in the absence of renal disease. Mean patient age was 58.1 years. Tumours were small (mean size: 2.4 cm) and classified as pT1. Histological characteristics consisted of tubules and papillae lined by a single layer of small clear cells harbouring low‐grade nuclei (Fuhrman grades 1 or 2). Architectural variations, with compact areas (41% of cases) and a micro‐ or macrocystic pattern (67% of cases) were observed frequently. Immunostaining demonstrated diffuse, strong expression of cytokeratin 7 and vimentin, whereas CD10, racemase, RCC antigen, translocation factor E3, TFE3 and translocation factor EB were consistently negative. In seven tumours, array‐CGH detected no chromosomal imbalances. Conclusions: Clear‐cell papillary renal cell carcinoma (ccpRCC) were differentiated from other renal neoplasms by a specific constellation of histopathological and immunohistochemical features, without characteristic genomic imbalances. Clinical, histopathological and genomic data suggested that these tumours have a low potential for malignancy.     

Morbidity of patients with analgesic-associated nephropathy on regular dialysis treatment and after renal transplantation

Summary In a retrospective study, patients with end-stage renal failure from analgesic-associated nephropathy — 55 on regular dialysis treatment and 12 after renal transplantation — were under observation for 57 and 33 months, respectively. Of these 34 patients on chronic hemodialysis had suffered from different cardiovascular diseases. Hypertriglyceridemia was diagnosed in 62% of the patients, arterial hypertension requiring antihypertensive therapy in 44%. In three patients (5%) carcinoma of the urinary bladder were diagnosed. The leading causes of death in 21 patients included cardiovascular diseases (29%), hyperkalemia (19%), sepsis, and malignant tumors (14% each). Rejection occurred in 3 out of 12 patients after renal transplantation. Again, cardiovascular morbidity was high (58%) with coronary heart disease being present in 33% of the patients. Hypertriglyceridemia was observed in 5 out of 6 patients, antihypertensive therapy was needed in 50%. One patient died from primary pulmonary hypertension.     

Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.