[The Early Years of Nephrology at Molinette Hospital in Turin Told by Those Who Lived and Built Them].

This article, written by several authors, describes the birth and early development of the nephrology at Molinette Hospital in Torino, Italy. In particular, it supplies important information on Antonio Vercellone, very motivated and innovative clinician and one of the fathers of Italian nephrology, and on Giuseppe Piccoli, his right-hand man and then his successor. This article also shows the strong professional and human engagement that was requested to the young doctors who, in the early Sixties and Seventies of the past century, had chosen to devote their professional lives to the patients with kidney diseases: from endless workdays without schedules to the anguish caused by the shortage of artificial kidneys to the cure of very fragile and unfortunate patients, and much more.

Letter to the Editor re: Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections?

UNLABELLED: In a recent paper, the authors oppose the opinion that " intra-arterial administration of iodinated-based contrast media (CM) appears to pose a greater risk of contrast-induced nephropathy (CIN) than intravenous administration" . As nephrologists, we are happy to have the opportunity to offer our expertise in the setting of renal disease aimed at optimizing diagnostic algorithm and preventive strategies. Our comment relies on the fact that, from a nephrologist's point of view, there is no doubt that renal damage following CM intra-venous administration in patients not in intensive care or emergency department and treated with conventional preventive strategies not only occurs with low frequency, but also appears of negligible clinical impact; it is confined to an asymptomatic increase of serum creatinine of 25% or 0.5 mg/dL lacking any prognostic negative impact, and in some case not significantly different from controls.True CIN, just related to intravenous CM injection for diagnostic purpose, has to be differentiated from all the other cause of renal involvement in people stricken with sudden and acute illness also receiving intra-arterial CM injection, in order to avoid patients being denied necessary radiological examinations due to an inappropriate fear of risk. KEY POINTS: • Contrast induced nephropathy (CIN) is not any nephropathy following contrast medium(CM). • CIN should only refer to renal damage strictly due to CM infusion. • True CIN following CM intravenous infusion is a clinically insignificant event. • Renal damage following intra-arterial CM infusion in compromised patients is not CIN. • Patients should not forego necessary radiological examinations for inappropriate understanding about risk.

Recognizing purple bag syndrome at first look.

Purple urine bag syndrome is a clinical entity first described in 1978. Its typical discoloration is worrying for clinicians. In the past, these patients sometimes reached the emergency unit only because of this exceptional worrying urinary sign and underwent invasive diagnostic examinations including cystoscopy, without any abnormal finding. It is now clear that this astonishing phenomenon of double discoloration of the urine, appearing purple in the bag and dark blue in the test tube, results from the formation of 2 different pigments (indirubin and indigo) in very alkaline urines due to enzymes produced by gram-negative bacteria, such as indoxyl phosphatase/sulfatase, which can convert urinary metabolites of dietary tryptophan. Practicing physicians should identify purple urine bag syndrome as a usually benign medical condition diagnosed in asymptomatic patients, which only requires treatment of bacteriuria with antibiotics, prevention of constipation, substitution of catheter and acidification of the urine. After these measures, urine typically returns to its normal color.

Renal outcome and monoclonal immunoglobulin deposition disease in 289 old patients with blood cell dyscrasias: a single center experience.

Monoclonal components (MC) formed by chains/fragments of intact/truncated globulin components produced in different lymphoproliferative diseases are responsible for monoclonal immunoglobulin deposition disease (MIDD) and consequent tissue damage by organized (amyloid fibrils) or non-organized (amorphous) deposits. The kidneys are the most commonly affected organs in MIDD, and renal failure represents an important adverse factor for prognosis. The renal outcome and the role of renal pathology in diagnosing MIDD was evaluated in 289 elderly patients with multiple myeloma (MM, n=115) and monoclonal gammopathy (MGUS, n=174). Renal impairment was the only significant risk factor for patient death, while significant risk factors for renal impairment were diabetes (HR 3.65, 95% CI: 2.08-6.41), light chain (LC) proteinuria (HR 2.18; 95% CI: 1.10-4.32) and type of MC (p=0.0019). Renal pathology documented MIDD in 12/30 cases (40%): six cases of AL-amyloidosis, two of LC disease, one of heavy chain disease and three of cast nephropathy, as well as four cases of glomerulonephritis, eight of arteriolosclerosis and six of normal picture. Main conclusions are that diabetes, sharing common glomerular damage with LC disease, is the strongest risk factor for progression of renal disease, and glomerular proteinuria or heavy LC proteinuria should raise a strong suspicion index of MIDD and prompt pathology assessment to reach the correct diagnosis.

Decreased kidney function and crystal deposition in the tubules after kidney transplant.

Adenine phosphoribosyltransferase (APRT) deficiency is an autosomal recessive purine enzyme defect that results in the inability to utilize adenine, which consequently is oxidized by xanthine dehydrogenase to 2,8-dihydroxyadenine (2,8-DHA), an extremely insoluble substance eventually leading to crystalluria, nephrolithiasis, and kidney injury. We describe a case of APRT deficiency not diagnosed until the evaluation of a poorly functioning kidney transplant in a 67-year-old white woman. After the transplant, there was delayed transplant function, urine specimens showed crystals with unusual appearance, and the transplant biopsy specimen showed intratubular obstruction by crystals identified as 2,8-DHA using infrared spectroscopy. APRT enzymatic activity was undetectable in red blood cell lysates, and analysis of the APRT gene showed 1 heterozygous sequence variant, a duplication of T at position 1832. The patient was treated with allopurinol, 300 mg/d, and transplant function progressively normalized. Because patients with undiagnosed APRT deficiency who undergo kidney transplant may risk losing the transplant because of an otherwise treatable disease, increased physician awareness may hasten the diagnosis and limit the morbidity associated with this disease.

Structure-activity relationships of low molecular weight heparins expose to the risk of achieving inappropriate targets in patients with renal failure.

Heparins are used in "therapeutic doses" for systemic anticoagulation to treat patients who have confirmed venous thromboembolism, or in "prophylactic doses "for the prevention of venous thromboembolism: they are generally lower doses and are employed once a day. Structure-function relationships are strongly influenced by the chain length of the molecules. In fact, unfractionated heparin (UFH) binds to ATIII lysine site leading to a conformational change of the ATIII arginine reactive centre able to create a covalent binding to the active centre serine of thrombin in a ternary complex formation composed by heparin, ATIII and thrombin. On the other side, low molecular weight heparins (LMWHs) are too short to be able to form this ternary complex, and mainly exert their anticoagulant effect by binding the factor Xa, always via ATIII. Lastly, the short unique pentasaccharidic sequence which is crucial for heparin's activity and has been recently synthesized as Fondaparinux, only acts via the formation of the high affinity ternary complex with ATIII-factor Xa. Due to their structure-function relationships, LMWHs cannot be monitored by conventional coagulation test used for monitoring UFH and need more specific anti-factor Xa activity determinations, but monitoring has been considered unnecessary in the general population due to a predictable dose/effect ratio. However, a disturbing rise of bleeding complications in patients with renal failure treated with LMWH has been published in the last years, that is explained by the accumulation of LMWHs in this setting, due the consequences of structure-metabolisms relationships of the small members of the heparin's family. In this context, physicians are often left to a "best guess" method of empiric dose adjustment, which is at risk of achieving inappropriate targets, with a percentage of values above and below target of 51% and 34%, respectively, depending on LMWHs dosage, body mass index and renal function. Without anti-Xa activity monitoring, the quality of care delivered in the setting of renal failure is poor, as over-prophylaxis can result in potentially dangerous anticoagulation, while under-prophylaxis can result in life-threatening thrombosis.

Gadolinium-associated nephrogenic systemic fibrosis: the need for nephrologists' awareness.

Nephrogenic systemic fibrosis (NSF) / nephrogenic fibrosing dermopathy (NFD) is a recently described disease, occurring only in patients with variable degrees of renal failure (RF) previously exposed to gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging. Public advisories are consistent on some key points including that no cases of NSF/NFD have been reported in patients with normal renal function, and GBCAs may be toxic in patients with RF due to the prolongation of the half-time allowing dissociation and extravasation of highly toxic gadolinium-free ions, potentially linked to the scleroderma-like NSF/NFD, a systemic disabling disease with a mortality rate of up to 30%. The most intriguing feature remains which cofactor might be at play to explain why the disease occurs only in a minority of exposed patients. Therefore, renal dysfunction (substrate) and gadolinium chelates (trigger agent) are necessary but not sufficient. The challenge for nephrologists includes (a) evidence of transmetallation, such as gadolinium deposits in bone, increased urinary zinc excretion, iron-transferrin dissociation or "spurious hypocalcemia" in exposed people; (b) research for uremic cofactors such as increased serum calcium/phosphate, acidosis, use of phosphate-chelating agents able to act as efficient competitor ligands or other drugs; and (c) identification of at-risk patients (with moderate to severe renal dysfunction) and definition of the role of dialysis in removing gadolinium chelates, if any. Nephrologists are called to action to collect and organize information to identify cofactors for NSF/NFD, and therefore they must be aware of this new pathology, as the eye sees only what the mind knows.

Gadolinium-enhanced magnetic resonance imaging, renal failure and nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy.

First described in 2000, nephrogenic systemic fibrosis (NSF)/nephrogenic fibrosing dermopathy (NFD) is a recently defined and sometimes fatal condition that, so far, has occurred only in people with some degree of renal failure, either during the conservative phase of chronic renal disease, the dialysis phase, or the kidney transplantation phase. The association between NSF/NFD and gadolinium-based magnetic resonance (MR) examination is so strong that public health agencies have sent out warnings concerning the use of gadolinium-enhanced MR in patients with renal failure. The prolonged residence of some gadolinium-chelates in the uremic milieu may allow free toxic gadolinium released from its chelate to extravasate into the extravascular space where it may accelerate fibrillogenesis. The medical community must be apprised of the concern surrounding the use of gadolinium contrast agent in patients with even moderate renal failure, considering that the number of at risk persons is 20 times greater than that of patients needing dialysis/transplantation, remember that the risk is particularly high in patients with liver transplantation in the presence of functional renal impairment, and not to forget that MR examination remains one of the three pillars of molecular medicine.

Rubidium, salami and depression. You cannot have everything in life.

BACKGROUND: Depression may induce malnutrition, but, as a paradoxical hypothesis, malnutrition may induce depression. This relationship, of course, depends on how we define malnutrition. CURRENT KNOWLEDGE: Rubidium is a trace element strongly linked with depression, and is deficient in uremia sufferers. However, in uremic patients, rubidium deficiency is more evident during predialysis, as it is at least partially corrected during dialysis and after transplantation. It seems that diet restrictions might be the main cause of rubidium deficiency, as it is mainly found in red meat. CONCLUSION: If rubidium is found in salami, then the occasional slice could be more beneficial for people suffering from depression than taking a lot of medication.

Ciprofloxacin crystal nephropathy.

Ciprofloxacin is a widely used fluoroquinolone for the treatment of patients with complicated and uncomplicated infections. With rare exceptions, only immune-mediated interstitial nephritis was described, with direct renal damage reported only in case of overdose. Experimental studies indicated that crystalluria may be associated with the administration of this drug, but the likelihood that ciprofloxacin crystal nephropathy would occur in humans was believed to be very low on the basis of previous data showing that ciprofloxacin crystalluria depended on a urine pH greater than 6.8. However, we report 2 cases of ciprofloxacin crystal-induced nephropathy with a clinical pattern of acute reversible tubular damage and intratubular crystals identical to that previously described in elderly patients treated with ciprofloxacin dosages within therapeutic schedules. Crystals in the tubules were negative for both the von Kossa stain for phosphates and alizarin red stain for calcium.