Acute phosphate nephropathy after bowel cleansing: still a menace
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Santos, A. Branco, S. Silva, A. Paiva, J. Baldaia, J. Maximino, A. Loureiro, R. Henrique" "autores" => array:8 [ 0 => array:4 [ "Iniciales" => "P." "apellidos" => "Santos" "email" => array:1 [ 0 => "paulo.ads@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "Iniciales" => "A." "apellidos" => "Branco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "S." "apellidos" => "Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "Iniciales" => "A." "apellidos" => "Paiva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => array:3 [ "Iniciales" => "J." "apellidos" => "Baldaia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 5 => array:3 [ "Iniciales" => "J." "apellidos" => "Maximino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 6 => array:3 [ "Iniciales" => "A." "apellidos" => "Loureiro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 7 => array:3 [ "Iniciales" => "R." "apellidos" => "Henrique" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Nephrology Unit, Internal Medicine Department, Pedro Hispano Hospital, Matosinhos, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Department of Pathology, Portuguese Institute of Oncology, Porto, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10544_108_6841_en_10544_f1.jpg" "Alto" => 235 "Ancho" => 333 "Tamanyo" => 13060 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy. Von Kossa coloration (40x)." ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dear editor:</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Colonoscopy is critically dependent on adequate pre-procedural bowel cleansing and oral sodium phosphate bowel purgatives (OSP) have been used with good acceptance and efficacy for this purpose<span class="elsevierStyleSup">1</span>. Among others metabolic and clinical disturbances described after the procedure, acute kidney injury may be a serious complication<span class="elsevierStyleSup">2,3</span>. We present two cases of sodium phosphate induced acute renal failure.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 1</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara">A 84 year-old male with a past history of stage 3 obstructive chronic renal failure, prostatic hypertrophy and hypertension, medicated with losartan, presented with complaints of six months weigh loss and changed bowel habits.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">A colonoscopy was performed after preparation with oral sodium phosphate solution (Fleet phosphosoda<span class="elsevierStyleSup">®</span>) with standard dose and its result was normal.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">A week later, the patient reported pedal and orbital oedema and was observed on the emergency department. The physical examination was unremarkable except for hypertension (180/80 mmHg) and lower limbs oedema. Laboratory results showed haemoglobin 11.1 g/dl, serum urea 346 mg/dl, serum creatinine 9.2 mg/dl, serum sodium 130 mEq/L, serum potassium 6.5 mEq/L, serum phosphorus 6.6 mg/dl, normal serum calcium, serum bicarbonate 15 mEq/L and mild proteinuria. Serum and urine immunoelectrophoresis and immunologic study were normal. Renal ultrasound showed increased cortical echogenicity. Haemodialysis was initiated. Kidney biopsy showed minimal mesangial expansion. The tubules were mildly dilated and focal interstitial fibrosis was present. Von Kossa stain positive deposits were observed within the cytoplasm of tubular epithelial cells, tubular lumen and interstitium (figure 1 and figure 2). Immunofluorescence was negative for immunoglobulin or complement.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">We made the diagnosis of acute phosphate nephropathy secondary to administration of a sodium phosphate purgative.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Renal dysfunction didn’t improve after 7 months and the patient continues on regular haemodialysis.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 2</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">A 88 year-old male with a past history of prostatic hypertrophy and marginal zone-B cell lymphoma IV-B stage (treated with vincristine, cyclophosphamide and prednisolone for two cycles followed by second line therapy with rituximab and chlorambucil with disease progression) and stage 4 obstructive chronic renal failure. A virtual colonoscopy was performed after bowel preparation with Fleet phosphosoda<span class="elsevierStyleSup">®</span>. Colonic diverticulosis was diagnosed.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Five days latter the patient reported lethargy and anuria and was admitted on the emergency department. He presented with drowsiness and was hypotensive, apyretic and oliguric. He presented inspiratory crackles on chest exam, distended and painful abdomen without guarding and lower limb oedema. Abnormal test results were hemoglobin 9.7 g/dL, leucocytes 17.1 x 10<span class="elsevierStyleSup">9</span>/L (87% neutrophils), platelets 70 x 10<span class="elsevierStyleSup">9</span>/L, serum creatinine 3.45 mg/dL, serum urea 106 mg/dL, serum calcium 4.5 mg/dl, serum phosphorus 18.3 mg/dL, lactate dehydrogenase 3,028 U/L, c-Reactive protein 28.2 mg/dL, pH 7.3, bicarbonate 13.3 mEq/L and lactate 7.5 mmol/L; Urine dipstick was positive for blood, leucocytes and proteins. Renal ultrasound showed kidneys with enhanced echogenicity. Chest radiograph showed interstitial oedema and abdominal radiograph was normal.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Suspected severe urinary sepsis and acute kidney injury secondary to sepsis and phosphate nephropathy were assumed. Intravenous fluid was started, samples were obtained for culture and broad spectrum antibiotics were started. There was no clinical improvement and conservative measures were adopted.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Acute phosphate nephropathy (AphN) is a form of kidney injury that occurs after the use of bowel purgatives that contain oral sodium phosphate (OSP)<span class="elsevierStyleSup">2</span>. OSP bowel solution (Fleet phosphosoda<span class="elsevierStyleSup">®</span>) is a hyperosmotic purgative that has been used with good acceptance and efficacy in bowel cleansing before colonoscopy<span class="elsevierStyleSup">1</span>. Both patients made the standard regimen (two 45 ml doses taken 10-12 h apart). Each dose contains monobasic and dibasic sodium phosphate providing the equivalent of 5,8 g of elemental phosphorus and 5 g of sodium<span class="elsevierStyleSup">3</span>. Intestinal absorption occurs and transient hyperphosphatemia and hypocalcemia are found in all patients<span class="elsevierStyleSup">2</span>. However, severe hyperphosphatemia, symptomatic hypocalcemia, hypernatremia, symptomatic hyponatremia, hypokalemia, anion-gap acidosis and acute kidney injury have been described after the procedure<span class="elsevierStyleSup">3-6</span>. Two different clinical patterns of OSP-induced acute kidney injury have been described: early symptomatic and late insidious<span class="elsevierStyleSup">2</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The earlier form consists in an acute illness that manifests as changes in mental status, tetany, or cardiovascular collapse, usually in hours of bowel preparation, and patients present with severe hyperphophatemia and hypocalcemia. The second patient presented fit in this category. These patients require urgent fluid resuscitation, rapid correction of electrolyte disturbances, and sometimes dialysis. Despite aggressive fluid replacement and resuscitation our patient died. Some patients with this presentation survive and show renal function recovery<span class="elsevierStyleSup">2</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The second form is due to AphN with a more insidious onset (days to months) and is generally irreversible<span class="elsevierStyleSup">1</span>. At the time of diagnosis, serum phosphorus and calcium levels are normal, unless measured within 3 days of bowel preparation. This was in fact the case of the first patient. As we found, the main pathologic finding in kidney biopsy is nephrocalcinosis demonstrated with the Von Kossa stain<span class="elsevierStyleSup">1</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Following reports of AphN Fleet phosphosoda<span class="elsevierStyleSup">®</span> was voluntary withdrawn from US market in 2008<span class="elsevierStyleSup">10</span>. However OSP solution is still in use in some countries, as Portugal.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The pathophysiology of APhN involves transient hyperphospatemia, volume depletion exacerbated by concurrent ACE-I, ARB and diuretics, and elevated distal tubular phosphate and calcium concentrations<span class="elsevierStyleSup">1,8,10</span>. Risk factors include advanced age, chronic kidney failure, dehydratation, female gender, diuretics, a history of colitis, and, probably, diabetes mellitus and non-steroidal anti-inflammatory drugs<span class="elsevierStyleSup">1,10</span>. Data indicate a high risk for chronic renal failure<span class="elsevierStyleSup">1,9,10</span>. Our first patient needed long term haemodialysis. In Markowitz series none patient returned to their baseline creatinine levels and 19% progressed to ESRD at mean of 13.8 months after colonoscopy<span class="elsevierStyleSup">9</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">In conclusion, these cases highlight the importance of AphN because such OSP are still used in clinical practice. Clinical presentation may assume two forms and, in any of these, consequences are serious and sometimes fatal. Strategies to prevent the development of APhN should be adopted and include avoidance in high-risk patients, adequate hydratation, dose minimization,  increasing the interval between doses and possibly not administering ACE-I, ARB, diuretics and NSAID on the day before and the day after colonoscopy procedure<span class="elsevierStyleSup">6,10</span>. It is also advisable to perform serum biochemistry tests after the procedure, in order to detect any renal or electrolyte abnormalities<span class="elsevierStyleSup">7</span>.</p><p class="elsevierStylePara"><a href="grande/10544_108_6841_en_10544_f1.jpg" class="elsevierStyleCrossRefs"><img src="10544_108_6841_en_10544_f1.jpg" alt="Kidney biopsy. Von Kossa coloration (40x). "></img></a></p><p class="elsevierStylePara">Figure 1. Kidney biopsy. Von Kossa coloration (40x). </p><p class="elsevierStylePara"><a href="grande/10544_108_6843_en_10544_f2.jpg" class="elsevierStyleCrossRefs"><img src="10544_108_6843_en_10544_f2.jpg" alt="Kidney biopsy. Von Kossa coloration (100x)."></img></a></p><p class="elsevierStylePara">Figure 2. Kidney biopsy. Von Kossa coloration (100x).</p>" "tienePdf" => false "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10544_108_6841_en_10544_f1.jpg" "Alto" => 235 "Ancho" => 333 "Tamanyo" => 13060 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy. Von Kossa coloration (40x)." ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10544_108_6843_en_10544_f2.jpg" "Alto" => 236 "Ancho" => 333 "Tamanyo" => 22102 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 0 | 11 |
| 2024 October | 54 | 0 | 54 |
| 2024 September | 72 | 0 | 72 |
| 2024 August | 67 | 0 | 67 |
| 2024 July | 59 | 0 | 59 |
| 2024 June | 54 | 0 | 54 |
| 2024 May | 67 | 0 | 67 |
| 2024 April | 44 | 0 | 44 |
| 2024 March | 55 | 2 | 57 |
| 2024 February | 58 | 12 | 70 |
| 2024 January | 47 | 7 | 54 |
| 2023 December | 30 | 8 | 38 |
| 2023 November | 49 | 13 | 62 |
| 2023 October | 38 | 15 | 53 |
| 2023 September | 50 | 12 | 62 |
| 2023 August | 71 | 6 | 77 |
| 2023 July | 41 | 9 | 50 |
| 2023 June | 48 | 7 | 55 |
| 2023 May | 62 | 10 | 72 |
| 2023 April | 23 | 3 | 26 |
| 2023 March | 57 | 3 | 60 |
| 2023 February | 39 | 6 | 45 |
| 2023 January | 65 | 1 | 66 |
| 2022 December | 51 | 3 | 54 |
| 2022 November | 48 | 5 | 53 |
| 2022 October | 44 | 3 | 47 |
| 2022 September | 56 | 7 | 63 |
| 2022 August | 49 | 6 | 55 |
| 2022 July | 30 | 2 | 32 |
| 2022 June | 44 | 5 | 49 |
| 2022 May | 46 | 4 | 50 |
| 2022 April | 43 | 1 | 44 |
| 2022 March | 56 | 3 | 59 |
| 2022 February | 42 | 1 | 43 |
| 2022 January | 47 | 4 | 51 |
| 2021 December | 55 | 7 | 62 |
| 2021 November | 57 | 3 | 60 |
| 2021 October | 81 | 3 | 84 |
| 2021 September | 42 | 9 | 51 |
| 2021 August | 47 | 1 | 48 |
| 2021 July | 62 | 7 | 69 |
| 2021 June | 50 | 4 | 54 |
| 2021 May | 78 | 1 | 79 |
| 2021 April | 332 | 4 | 336 |
| 2021 March | 77 | 16 | 93 |
| 2021 February | 67 | 5 | 72 |
| 2021 January | 85 | 8 | 93 |
| 2020 December | 62 | 2 | 64 |
| 2020 November | 41 | 5 | 46 |
| 2020 October | 40 | 5 | 45 |
| 2020 September | 31 | 2 | 33 |
| 2020 August | 30 | 7 | 37 |
| 2020 July | 27 | 5 | 32 |
| 2020 June | 30 | 3 | 33 |
| 2020 May | 44 | 7 | 51 |
| 2020 April | 36 | 9 | 45 |
| 2020 March | 44 | 12 | 56 |
| 2020 February | 27 | 8 | 35 |
| 2020 January | 39 | 12 | 51 |
| 2019 December | 48 | 16 | 64 |
| 2019 November | 26 | 9 | 35 |
| 2019 October | 9 | 3 | 12 |
| 2019 September | 16 | 12 | 28 |
| 2019 August | 13 | 7 | 20 |
| 2019 July | 17 | 12 | 29 |
| 2019 June | 18 | 5 | 23 |
| 2019 May | 15 | 2 | 17 |
| 2019 April | 51 | 10 | 61 |
| 2019 March | 24 | 11 | 35 |
| 2019 February | 20 | 9 | 29 |
| 2019 January | 28 | 12 | 40 |
| 2018 December | 88 | 20 | 108 |
| 2018 November | 98 | 14 | 112 |
| 2018 October | 77 | 36 | 113 |
| 2018 September | 48 | 10 | 58 |
| 2018 August | 33 | 16 | 49 |
| 2018 July | 43 | 12 | 55 |
| 2018 June | 47 | 15 | 62 |
| 2018 May | 53 | 17 | 70 |
| 2018 April | 56 | 3 | 59 |
| 2018 March | 61 | 12 | 73 |
| 2018 February | 51 | 9 | 60 |
| 2018 January | 43 | 8 | 51 |
| 2017 December | 61 | 8 | 69 |
| 2017 November | 58 | 9 | 67 |
| 2017 October | 43 | 12 | 55 |
| 2017 September | 38 | 9 | 47 |
| 2017 August | 36 | 7 | 43 |
| 2017 July | 48 | 9 | 57 |
| 2017 June | 41 | 5 | 46 |
| 2017 May | 62 | 13 | 75 |
| 2017 April | 39 | 3 | 42 |
| 2017 March | 34 | 7 | 41 |
| 2017 February | 33 | 10 | 43 |
| 2017 January | 37 | 6 | 43 |
| 2016 December | 82 | 6 | 88 |
| 2016 November | 98 | 14 | 112 |
| 2016 October | 124 | 10 | 134 |
| 2016 September | 162 | 2 | 164 |
| 2016 August | 196 | 0 | 196 |
| 2016 July | 181 | 0 | 181 |
| 2016 June | 108 | 0 | 108 |
| 2016 May | 155 | 0 | 155 |
| 2016 April | 115 | 0 | 115 |
| 2016 March | 88 | 0 | 88 |
| 2016 February | 111 | 0 | 111 |
| 2016 January | 127 | 0 | 127 |
| 2015 December | 127 | 0 | 127 |
| 2015 November | 78 | 0 | 78 |
| 2015 October | 57 | 0 | 57 |
| 2015 September | 70 | 0 | 70 |
| 2015 August | 72 | 0 | 72 |
| 2015 July | 70 | 0 | 70 |
| 2015 June | 33 | 0 | 33 |
| 2015 May | 69 | 0 | 69 |
| 2015 April | 14 | 0 | 14 |
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