The idiopathic nephrotic syndrome in the adult patient is the clinical situation that classically requires the performance of renal biopsy, which is justified by the fact that several histological entities can give rise to the syndrome in adults, each of which is associated with its own therapeutic protocols, differing from each other in terms of drugs, dosages, and duration of treatment. Richards et al. (1994) documented that renal biopsy, performed in adults with the nephrotic syndrome, significantly influenced the choice of therapeutic protocol in 86 % of the cases. On the other hand, conflicting opinions exist regarding the significance of histological findings for each single glomerular pathology. Regarding the nephrotic syndrome secondary to membranous glomerulopathy, some studies have indicated that the copresence of focal and segmental glomerulosclerosis (FSGS) is a negative prognostic indicator, both in terms of clinical response to standard therapy and of progression to renal failure (Dumoulin et al. 2003). Other studies, in contrast, have not found that FSGS or other histological variants of membranous nephropathy are as useful as clinical data in predicting the disease outcome (Troyanov et al. 2006). Regarding segmental glomerulosclerosis itself, numerous studies have stressed the importance of the histological characteristics of the biopsy obtained at the first signs of the disease. The presence of the cellular form, and its “collapsing” variant, indicates an inadequate response to conventional therapy and a faster progression towards end-stage renal disease (ESRD), in comparison with the classical histological variants including perihilar sclerosis and tip lesion (Stokes et al. 2006; Chun et al. 2004). The cellular variant is also highly predictive of segmental glomerulosclerosis recurrence posttransplant (Newstead 2003). Other, less frequent, diagnostic possibilities of the nephrotic syndrome may surprise the nephrologist as he or she reads the outcome of the biopsy, such as primary amyloidosis, fibrillary glomerulonephritis, membranous nephropathy with characteristics of lupus nephritis without the clinical or serological signs of systemic disease, and finally rare diseases with peculiar histological characteristics such as Fabry’s disease, collagen fibrotic glomerulopathy, and L-CAT (lecithin–cholesterol acyltransferase) deficiency nephropathy. In pediatric patients with the nephrotic syndrome, renal biopsy is not usually indicated since more than 90 % of these patients have minimal change glomerulopathy that usually responds to well-known corticosteroid protocols. Thus, renal biopsy in children is reserved for atypical presentations, such as the persistence of microhematuria, hypertension and low complement levels after 6 weeks of steroid therapy, and therapy failure, or for suspected congenital familial nephrotic syndrome.

In the absence of data clearly indicating the cause of acute renal failure (thus excluding cases with clear laboratory or radiological evidence of prerenal failure, obstruction, and acute tubular necrosis), renal biopsy becomes a fundamental tool not only for diagnosis but above all for prognosis and for determining the therapeutic protocol. One prospective study has shown that renal biopsy was essential in deciding the treatment and hence the outcome in 71 % of acute renal failure patients; the modification of the therapeutic strategy subsequent to the biopsy resulted in clinical benefits which far outweighed the risk of the biopsy (Kobrin and Madaio 1996).

The causes of renal allograft dysfunction correlate with the time from transplantation in which they are found; nevertheless renal biopsy can be essential for determining the diagnosis and the treatment choices.

The failure of the kidney to function immediately following transplantation is termed delayed graft function, which is formally defined as the persistence of oliguria or the need for dialysis in the first week posttransplant. Apart from urinary tract obstruction, caused by ureteral necrosis or obstruction, or from thrombosis of the renal artery or vein which can be diagnosed by Doppler ultrasonography, the cause of delayed graft function, and in particular the differential diagnosis between postischemic acute tubular necrosis (the most common cause of delayed graft function) and acute rejection, can only be determined by biopsy.

Early posttransplant renal dysfunction is characterized by renal insufficiency 1–12 weeks after transplantation in patients with initial normal functioning of the graft. The major causes of early dysfunction include acute rejection, calcineurin inhibitor (cyclosporine or tacrolimus) nephrotoxicity, urinary tract obstruction, or reduced renal perfusion associated with a reduction in effective circulating volume. Other diagnostic possibilities include infections (cytomegalovirus or polyoma virus) and early recurrence of the primary renal disease such as segmental glomerulosclerosis, hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura, Goodpasture’s syndrome (antiglomerular basement membrane antibody disease), and interstitial nephritis (Josephson et al. 1999). If one can exclude calcineurin inhibitor toxicity (by briefly reducing the dose and not seeing an improvement in renal function) and urinary tract obstruction, renal biopsy would be highly indicated.

Late acute graft dysfunction is characterized by abrupt worsening of renal function more than 3 months after transplantation. The causes of this situation are essentially the same as those of early posttransplant renal dysfunction, plus the possibility of noncompliance, especially in the case of adolescent recipients. A negative renal ultrasound, particularly the absence of renal artery stenosis, indicates the performance of the allograft biopsy.

Many patients suffer a gradual deterioration of renal function in the years following transplantation, often with persistent proteinuria and hypertension. In this situation, in cases where there is a suspicion of disease recurrence or de novo glomerulonephritis vs. chronic allograft nephropathy or drug nephrotoxicity, renal biopsy can provide valuable information (Briganti et al. 2002), particularly if one is contemplating the conversion of the immunosuppressive regimen.

Renal biopsy is not currently indicated, at least in common clinical practice, in patients who present with isolated proteinuria less than 500 mg to 1 g per 24 h, normal renal function, absence of hematuria of glomerular origin (see below), and absence of clinical or laboratory signs suggestive of systemic disease associated with glomerular pathology, such as systemic lupus erythematosus, vasculitis, monoclonal gammopathy, etc. In such cases the prognosis is good in terms of renal function, and there is no indication for therapy with steroids or other immunosuppressants. Current nephrological opinion changes, however, for proteinuria consistently and significantly greater than 1 g per day, particularly when there is an insufficient response to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers; in these cases most nephrologists opt for biopsy. The presence of diabetes mellitus, in particular in the absence of other signs of microangiopathy such as retinopathy, does not always justify the clinical diagnosis of diabetic nephropathy. Studies carried out on patients with diabetes mellitus type 2 and proteinuria have shown that between 10 and 30 % of cases result from nephropathy different from classical diabetes (Fioretto et al. 2008), and thus, also in the presence of diabetes and proteinuria, renal biopsy should be considered to optimize the therapeutic approach.

Patients who present with isolated glomerular hematuria (dysmorphic red cells and/or red cell casts in the urinary sediment, dipstick negative for proteinuria, normal renal function, normal blood pressure) usually have a benign prognosis in terms of renal function and do not require drug therapy or particular restrictions in terms of lifestyle. In these cases in which prognostic information is not forthcoming and the nephrologist is not confronted with the necessity of making therapeutic choices, renal biopsy does not appear to be indicated. One series of patients with these clinical characteristics in which renal biopsy was performed demonstrated thin membrane disease in 43 % of cases, IgA nephropathy in 20 %, other glomerular pathology (including Alport’s syndrome) in 19 %, and histologically normal kidneys in 18 % (Hall et al. 2004). In another series renal biopsy modified the therapeutic strategy in only 3 % of cases (Richards et al. 1994). An exception could be made for cases of isolated glomerular hematuria associated with a family history of renal disease and particularly of chronic kidney injury. When the patient in question is young, renal biopsy may have a role in genetic counseling. In cases in which the hematuria is associated with nonnephrotic proteinuria, the probability of significant glomerular pathology is greater than 70 %, and in particular the probability of finding IgA nephropathy is greater than 40 % (Hall et al. 2004); in this situation, performance of renal biopsy should be considered.

Renal biopsy may have an important diagnostic role also when the patient presents with established chronic renal injury. The leading example is when renal cortical thickness, demonstrated by ultrasound, is greater than 8–10 mm (Barbiano Di Belgiojoso et al. 2002), particularly associated with proteinuria but also in the absence of proteinuria. In patients with proteinuria, renal biopsy may identify the glomerular disease responsible for the proteinuria, modify the therapy accordingly, quantify the degree of chronicity of the lesion as a useful prognostic indicator, and demonstrate pathology which may be destined to recur in a possible future kidney transplant (Pasquali 2008; Lupo et al. 2008). In patients with chronic kidney injury without proteinuria, renal biopsy can also play an important diagnostic role with therapeutic implications, as well as in defining the chronicity index and the prognosis. An important example is when the biopsy demonstrates an interstitial nephritis which may be susceptible to corticosteroid treatment (Tomson Charles 2003).