How potassium balance is maintained in the face of nephrotic syndrome is demonstrated by Fila et al. (2011) in the current issue of The Journal of Physiology. The kidneys filter 180 litres of fluids per day. In the healthy human being, less than 2% of the initial filtrate is actually excreted. Kidney anatomy is such that larger molecules cannot readily pass the filtration border. Therefore, the urine of healthy individuals contains very little to no protein. Once a certain amount of proteins appear in the urine we speak of proteinuria. Over the last few years it has become evident that proteinuria is a reliable predictor of chronic kidney disease and even slight proteinuria is a risk factor for developing end-stage renal disease (Iseki et al. 2003). In many countries, end-stage renal disease is dramatically increasing, such as in the UK, where cases have doubled over the latest decade (Meguid El & Bello, 2005). The vast extent of end-stage renal disease is threatening to become an epidemic, and due to the sophisticated care required, e.g. dialysis, not only the individual patients but entire society faces catastrophe. Nine out of ten patients with treated end-stage renal disease stem from the higher developed countries reflecting the economic scale of the problem in treating these patients. So is there any good news? Indeed, it is surprising that so many open questions have remained in spite of the social economic dimensions of proteinuria. When proteins are filtered into the tubular network of the kidney water follows, thus causing volume depletion in the diseased subject. In order to counteract the volume loss, the fluid-retaining hormones aldosterone and vasopressin are released, which enhance sodium and water uptake. For a long time it has been wondered why this compensatory response (predominantly mediated by aldosterone) is exaggerated. Hypernatriaemia is commonly observed in patients with protein loss. Thus, oedema forms in various body compartments including the peritoneum. The combination of proteinuria and oedema are key features of the so-called nephrotic syndrome. Currently, we have a rather good picture of how proteinuria comes about, i.e. how the filtration barrier is affected. However, it remains unclear why sodium retention may overshoot. It was the pioneering work of Svenningsen et al. (2009) that demonstrated an intriguing signalling cascade promoting sodium retention. Among the proteins filtered into the tubular network is plasminogen. Plasminogen is converted to plasmin by urokinase-type plasminogen activator which then activates the epithelial sodium channels (ENaC) by cleavage of the γ ENaC subunit. Besides this being a remarkable demonstration of how filtered proteins can affect tubular function, shedding light on the sodium-retaining mechanisms raised a new equally important question: Normally, sodium is taken up in exchange for potassium. Thus, sodium retention should be accompanied by hypokaliaemia. Hypokaliaemia would have serious consequences on neuromuscular excitability and would therefore constitute a life-threatening side-effect of proteinuria. It is here that the present article from Fila et al. adds to our understanding. The authors investigated why urinary potassium loss is not taking place in the nephrotic syndrome rat. Interestingly, isolated collecting ducts from nephrotic syndrome rats experienced a down-regulation of the potassium channel (renal outer medullary potassium channel, ROMK), thus preventing potassium elimination. Consequently, in the whole animal model, nephrotic rats could not adequately excrete potassium when placed on a potassium-rich diet due to this down-regulation of ROMK. The impaired potential of maintaining potassium balance in nephrotic syndrome is of considerable clinical importance. Obviously, the organism prevents excessive potassium loss in the face of proteinuria by down-regulation of potassium channels in the collecting ducts of the kidney. However, should nephrotic syndrome patients experience a potassium-rich diet, they no longer have the full capacity to eliminate potassium, thus leading to hyperkalaemia. Therefore it is important not only to restrict sodium in the diet of patients with nephrotic syndrome, they should also be placed on a low-potassium diet. In analogy to plasmin being a mediator of sodium retention during nephrotic syndrome, it again seems to be abnormal protein occurence in the tubular fluid that may trigger the down-regulation of ROMK. This seems to happen via phosphorylation of ERK that arises from the tubular fluid proteins (e.g. albumin) present in nephrotic syndrome. In their truly translational study, Fila et al. also investigated the plasma potassium levels of nephrotic children admitted to the paediatric nephrology department. Indeed, it was confirmed that potassium balance is not altered in spite of the abnormal sodium levels and volume homeostasis. Taken together this is a unique demonstration of how the organism maintains normal potassium levels in plasma, in the light of profound changes in volume electrolyte homeostasis caused by nephrotic syndrome.